Androgens in Human Evolution
A New Explanation of Human Evolution
Abstract
Human evolution consists of chronological changes in gene regulation of a
continuous and relatively stable genome, activated by hormones, the production
of which are intermittently affected by endogenous and exogenous forces.
Periodic variations in the gonadal androgen, testosterone, and the adrenal
androgen, dehydroepiandrosterone (DHEA), significantly participated in all
hominid transformations. The hominid characteristics of early Australopithecines
are primarily a result of increased testosterone. The first significant cold of
the early Pleistocene resulted in an increase in DHEA that simultaneously
produced Homo and the robust Australopithecines. Subsequent Pleistocene climatic
changes and differential reproduction produced changes in DHEA and testosterone
ratios that caused extinction of the robust Australopithecines and further
changes in "Homo." Changes in testosterone and DHEA produce allometric and
behavioral changes that are identifiable and vigorous in modern populations.
Argument
Humans and chimpanzees differ in hormones that produce significant effects on
anatomy, physiology, and behavior. Human males and females produce more
testosterone than chimpanzee males and females, respectively (Winter et al.,
1980). Chimpanzee and human females produce similar levels of estradiol (Winter
et al., 1980) and progesterone (Hobson et al., 1976). I suggest early
differences in testosterone levels started species divergence and promoted
hominid evolution.
Testosterone
Estradiol and testosterone support different functions in females. Estradiol
stimulates genital displays that advertise ovulation in monkeys (Wilson, 1977),
gibbons (Nadler et al., 1993), chimpanzees (Ozasa & Gould, 1982) and gorillas
(Nadler, 1980), but not women. Estradiol and testosterone both peak near
ovulation in female orangutans, gorillas, chimpanzees and humans. Estradiol and
testosterone act synergistically to maximize reproduction. Estradiol prepares
the sexual apparatus for coitus and impregnation; testosterone stimulates sexual
activity.
While it "is a general trend in Western societies to blame psychosocial factors
for diminished sexuality in women," diminished sexual drive and other aspects of
sexual dysfunction, in androgen-deficit women, are primarily improved by
testosterone therapy (Davis, 1996; Kaplan & Owett, 1993). In postmenopausal
women, combined estrogen-androgen therapy significantly improves "sexual desire,
satisfaction and frequency," whereas estrogen alone, or estrogen-progestin
therapies do not, leading to the conclusions that "androgens play a pivotal role
in sexual function" and "estrogens are not a significant factor determining
levels of sexual drive and enjoyment" (Sarrel et al., 1998). Because estrogens
prepare female genitalia for coitus, it is best to treat sexual dysfunction in
women with testosterone and estradiol (Davis et al., 1995). Nevertheless, libido
is primarily an effect of testosterone. In sexually functional women,
testosterone treatment produces a "statistically significant increase in genital
responsiveness" and "subjective reports of 'genital sensations' and 'sexual
lust'" (Tuiten et al., 2000). Supplementary testosterone not only corrects
deficiencies in sexual desire, it intensifies normal sex drive.
Estradiol levels in women and chimpanzees are optimal. Therefore, increasing
testosterone to estradiol ratios in hominids increases sexuality
proportionately. As testosterone increases, so does the sexual activity of the
female. This increases male attendance and reproduction. These females have an
advantage in representation in future generations.
Increasing the testosterone to estradiol ratio reduces the effects of estradiol.
Human female fetal external genitalia contain AR (androgen receptors) and ER
(estrogen receptors), while male external genitalia lack ER (Kalloo et al.,
1993). The AR in the female external genitalia "were strikingly similar to that
in the male." In women, increased testosterone competes with the effects of
estradiol on external genitalia. As the testosterone to estradiol ratio
increases, the labial display decreases. This is why humans do not produce a
labial display. (Adrenal androgens stimulate male and female pubic hair just
prior to puberty and probably act through the common AR in both sexes.) The
primary sexual signal of female chimpanzees is the labial display. In women the
primary display of sexual maturity is the breast. Chimpanzee mothers and small
breasted women produce ample nutrition for nursing offspring. I suggest the
increased size of the human breast is a sexual signal. Breasts are
estradiol-dependent structures. Breast enlargement is a signal of maturing
estradiol levels, and may also be a signal of maturing testosterone levels and,
therefore, of increased sexual arousal.
Fat tissues capture steroid hormones, including testosterone. Testosterone is
aromatized to estradiol in fat tissues. While breast fat is not as active as
axillary fat in converting testosterone into estradiol, "results indicate a
possible role of adipose tissue as a significant extra-gonadal source of
estrogens" (Nimrod & Ryan, 1975). This increased level of estradiol in the
breast could increase breast size. Aromatization of testosterone occurs in
normal female breast tissue and in gynecomastia in men. Breast tissue from five
out of six men with gynecomastia aromatized testosterone into estradiol (Perel
et al., 1981). (Gynecomastia is true breast development in men, vis-à-vis
pseudogynecomastia caused by fat deposits.) Conversion of testosterone into
estradiol in human breast fat augments breast development and size. Testosterone
and estrogen both inhibit human hair production, in vitro (Kondo et al., 1990).
Increasing testosterone levels in hominids reduced hair production in both
sexes. The combined effects of testosterone and estradiol further reduce hair
growth in women. This increases the prominence of the breast. The female human
breast is a signal of mature estrogen and testosterone production. The female
human breast is largest among primates due to increased testosterone.
The pubic bones of male mice are shorter and thicker than those of female mice.
Neonatal testosterone treatment of female mice produces "pubic bones shorter and
thicker than those of age-matched females" and "Pubes in male mice castrated at
the day of birth were thinner than those of intact males." (Iguchi et al.,
1989). Androgens directly affect bone growth in women (Gasperino, 1995).
Testosterone is involved in bone growth and produces changes in the female
pelvis. Increasing testosterone in hominid females would change growth and
development of the pelvis with time. Essentially all tissues produce androgen
receptors, therefore growth and development of all tissues in emerging hominids
were affected by testosterone. The muscles that control upright walking
increased in strength as a result of increased testosterone. The large size of
the gluteus maximus "is one of the most characteristic features of the muscular
system in man, connected as it is with the power he has of maintaining the trunk
in the erect posture." (Gray, 1966).
The brain also enlarged as a response to the effects of increasing testosterone.
The brain produces androgen receptors throughout. Testosterone exposure of the
male human brain, in utero, results in increased head circumference of male
brains at birth (Liebermen L.S., 1982). Androgen treatment of female monkeys
increased performance to male levels, on an "object discrimination task." Both
male and female performance levels were adversely affected by lesions in the
orbital prefrontal cortex, indicating that "gonadal hormones may play an
inductive role in the differentiation of higher cortical function in nonhuman
primates." (Clark & Goldman-Rakic, 1989).
The single phenomenon of increasing testosterone produced the hominid
characteristics of Australopithecus. The single phenomenon of increased
testosterone production participated in every hominid characteristic,
simultaneously. Testosterone increased female sexual activity, reduced female
genital display, reduced hair growth, increased breast size, changed pelvic
growth, and produced increases in brain size. These combined changes accelerated
the advent of upright, bipedal locomotion and larger brains. (Male and female
pubic hair is visually different. It may be that pubic hair was the first
appreciable change in sexual display as body hair and the labial display
digressed in Australopithecus.)
The canine teeth of Australopithecus were smaller, and less "projecting" than
contemporary primates. However, in living monkeys, testosterone increases large
canine teeth. The canines are larger in males and prenatal exposure of females
to testosterone increases the size of their canines (Zingeser & Phoenix, 1978).
This appears to present a quandary for this explanation of human evolution.
Humans produce more testosterone, yet the canine teeth are small.
Dehydroepiandrosterone
In hominids the effects of testosterone, on brain size, teeth, and other
tissues, are due to changes in availability of DHEA. I suggest DHEA is involved
in growth and maintenance of all tissues, especially the brain, and is paramount
in the formation of the robust Australopithecines and Homo. DHEA is proven to
positively affect growth and function of many tissues, including the brain.
"Dehydroepiandrosterone and its sulphate ester are neuroactive and are both
imported into the brain from the circulation and produced in the nervous system.
These neurosteroids have neurotrophic and excitatory effects." (Baulieu, 1999).
(The enlargement of neural tissue during primitive evolution may be due to
increased absorption and production of DHEA.) Testosterone evolved after DHEA;
testosterone is a conversion product of androstenedione, which is a direct
conversion product of DHEA. Therefore growth before testosterone relied on DHEA.
Testosterone evolved because its molecular structure affected DNA in an
advantageous manner. My principal hypothesis is DHEA optimizes transcription and
replication of DNA. Therefore, a subordinate hypothesis suggests the advantage
of testosterone is that it directs DHEA use for genes that are targets of
testosterone action. Testosterone increases the rate of DHEA use. (Males produce
more testosterone, therefore, in males, testosterone-target-tissues are larger,
e.g., muscle, bone, etc., or grow at different rates, producing different
structures from the same beginning tissues, e.g., genitalia, or differences in
final brain function, e.g. male-female differences in the brain. Testosterone is
not the male hormone, males simply produce more.)
That testosterone affects levels of DHEA is supported by reductions of DHEA
during increased levels of testosterone in some nonhuman primates. The following
references support a pattern of decline of DHEA levels when testosterone levels
increase. In the crab-eating monkey, "DHA [DHEA] levels were high during the
first months, decreased at about 1 year, remained stable during infancy and
prepuberty and then declined again during puberty. At about 5 years, the values
were 28% of those in neonates." (Meusy-Dessolle & Dang, 1985). "By contrast the
serum prolactin and dehydroepiandrosterone levels showed an inverse pattern
achieving their highest levels in spring, during the period of reduced
testicular function." (Wickings & Nieschlag, 1980). "Serum testosterone levels
rose during male development; however, there was a progressive decrease in
dehydroepiandrosterone sulfate levels indicating the absence of adrenarche."
(Crawford et al., 1997). The decline in DHEA when testosterone is increased in
these examples could indicate that DHEA is being utilized in tissues, therefore
reducing measurable levels in blood.
In the Australopithecines, as in the primates above, a limited amount of DHEA
was directed toward one tissue at the expense of another. As testosterone
increased in Australopithecus, the brain increased use of DHEA. When
testosterone increased use of DHEA for the brain, the available DHEA for growth
and development of canine teeth was reduced. (The brain may be the paramount
tissue in vertebrate evolution because it is able to capture DHEA better than
other tissues.) The brain increased slightly and the canines decreased slightly.
Brain tissue simply takes more of the supply of DHEA; canines do not grow as
large in response. (Measurable levels of DHEA are very high in monkeys, much
lower in humans, with chimpanzees levels very similar to humans. I suggest this
is an indication of relative use of DHEA by the respective brains.)
The cold periods of the Pleistocene epoch directly caused changes in hominid
evolution. Homo and the robust Australopithecines are the results of the first,
large cold increase around 2.5 mya. A common phenomenon occurred in both. This
particular cold selected for individuals that produced more DHEA. Increased DHEA
is an advantage during cold. DHEA treatment in rats "affected body weight, body
composition and utilization of dietary energy by both impairing fat synthesis
and promoting fat-free tissue deposition and resting heat production."
(Tagliaferro et al., 1986). This effect of DHEA is due to increased
thermogenesis (Bobyleva et al., 1993). Individuals who produce more DHEA derive
more heat from the same nutrition. As cold decreased available nutrition,
individuals that could derive more benefit from sparse nutrition had a survival
advantage. The ratio of DHEA to testosterone in hominids started to change at
this time. (Increased DHEA may have been involved in early mammalian evolution.
That is, increased ability to make DHEA may have been the reason mammals
survived events that caused extinction of the dinosaurs.)
The Australopithecines remained relatively unchanged during the upper Pliocene.
The change from A. afarensis to A. africanus was probably due to increasing
testosterone. A noticeable change occurred in the Australopithecines during the
first cold of the early Pleistocene. The robust Australopithecines appeared,
i.e., robustus and boisei. Robustus and boisei differed from afarensis and
africanus mainly in teeth size and facial size, little in body size. Pronounced
sexual dimorphism continued in the Australopithecines, including the robust
types. That is, the survival strategy of these groups continued to mainly depend
on increased testosterone in males. The levels of testosterone did not increase
much, so brain size did not increase much. The cold selected for individuals of
higher DHEA in this group. Therefore, increased availability of DHEA increased
effects on testosterone-target-tissues. Teeth and facial structures are
testosterone-target-tissues. The available DHEA, not used in thermogenesis,
caused increased size in the teeth and facial structures. The testosterone
levels of the males did not change significantly, so their brain size did not
change significantly.
Homo differs from Australopithecus mainly in a small increase in brain size at
the time of separation of the two. I suggest separation of Homo from
Australopithecus occurred as a result of increased testosterone in Homo females.
It is in Homo that the true effects of increased testosterone began to increase
rapidly. The breast would increase in Homo and increase selection pressure for
those changes that produce more efficient bipedal locomotion. As testosterone
increased in Homo females, brain size continued to increase over that of
Australopithecus. When this increase in testosterone first began in Homo, there
should be transitional forms with larger brains, but which continued to exhibit
small bodies and sexual dimorphism, such as Homo rudolfensis and Homo habilis.
H. rudolfensis and habilis developed contemporaneously with A. robustus and
boisei.
As testosterone and DHEA increased during this time period, increases in growth
continued in the brain and began to affect growth of the body. Homo began to
increase in overall size. The effects of these two hormones increased as the
climate began to warm. (There is no selection pressure to reduce testosterone
and DHEA levels by relative warmth.) Reduced use of DHEA for thermogenesis
increased availability for body and brain growth. Homo ergaster and H. erectus
emerged at this time. It is the increase in females of higher testosterone that
produced Homo. It is first identifiable in Homo erectus/ergaster. Sexual
dimorphism declined in Homo erectus as a result of increased female size, not a
decline in male size. This increase in testosterone in both sexes, and the
increase in DHEA, would increase bone growth and length.
Treatment of rats with DHEA increases bone mineral density. "Treatment with DHEA
caused a 4-fold stimulation of serum alkaline phosphatase, a marker of bone
formation, while the urinary excretion of hydroxyproline, a marker of bone
resorption, was decreased by DHEA treatment." (Martel et al., 1998). DHEA
treatment of postmenopausal women stimulates increases in serum osteocalcin,
another marker of bone formation (Labrie, 1997). Adrenarche is the beginning of
the measurable increase of DHEA in humans that begins around five- or
six-years-of-age and increases rapidly until about age twenty. Adrenarche
continues for years prior to puberty. A significant amount of bone growth occurs
prior to the growth spurt of puberty. "Premature adrenarche" produces an
acceleration of bone age that was greater in males, and the appearance of
premature pubic hair in 93.8% of both sexes (Likitmaskul et al., 1995). The
testosterone conversion product, dihydrotestosterone (DHT), produces no
qualitative differences in bone growth, only a more rapid increase in bone
growth in vitro. DHEA and DHT both stimulated "cell proliferation and
differentiated functions, but the gonadal androgen DHT was significantly more
potent than DHEA." (Kasperk et al., 1997). Years of bone growth due to DHEA
occurs prior to puberty; testosterone rapidly increases and finalizes body
growth at puberty during the growth spurt. Testosterone and estradiol rapidly
increase the final development of bone. A direct connection of increased bone
formation in individuals of higher testosterone exists. Serum testosterone,
estradiol and bone density are higher in black women than white women (Perry et
al., 1996). Testosterone is significantly higher in black college students than
white college students (Ross et al., 1986). Black males and females consistently
exhibit greater mean levels of "areal and volumetric bone mineral density" "at
all skeletal sites" than Asians, Hispanics, and whites (Bachrach et al., 1999).
Increased testosterone increases bone growth. As testosterone and DHEA increased
in Homo, growth in size and length of bones increased.
Homo erectus existed during a time of relative warmth. This climate change means
that its DHEA could be used for purposes other than thermogenesis. The brain of
H. erectus doubled that of Australopithecus. There was less sexual dimorphism in
H. erectus than in the Australopithecines, but still more than that of later
hominids. Musculoskeletal development was very robust, another consequence of
additional DHEA for growth, not used by the brain or for thermogenesis. The
anterior teeth were larger and the molar teeth smaller than those of
Australopithecus. The decrease in posterior teeth results from an increase in
development of anterior parts of the brain. Brain forming later, during the time
of formation of posterior teeth, reduces available DHEA for those teeth,
therefore, they are smaller. Again, the brain takes DHEA at the expense of other
tissues.
The return of cold later in the Pleistocene returned selection for increased
DHEA. Neandertal habitat was characterized by relative containment. The cold and
containment increased DHEA and testosterone in Neandertal. Neandertal continued
to increase in brain size. The teeth and facial structures and brain development
of Neandertal are exaggerated due to increased testosterone and DHEA. The large
teeth and brains indicate there was plenty of DHEA for sharing between various
tissues. However, this large brain was increased in posterior regions, not in
anterior areas. This would be consistent with early puberty.
High testosterone and high DHEA could cause early puberty. Increased androgen
receptors in the brains of individuals of higher testosterone increase use of
DHEA for brain growth during childhood. This accelerates the onset of puberty,
because the brain structures that control puberty mature early. This shortens
the time to hypothalamic stimulation of testosterone production by the gonads.
As testosterone-target-tissues grow and begin to increase use of DHEA,
competition for available DHEA increases. Therefore, early puberty reduces
available DHEA for growth of anterior parts of the cerebrum. Large bodies and
early puberty reduce final (anterior) brain development. That is, early puberty
reduces the time of basic growth and development of the brain that occurs under
the influence of DHEA.
Effects of low testosterone on craniofacial growth and statural height have been
demonstrated in boys with delayed puberty. "These results show that statural
height and craniofacial dimensions are low in boys with delayed puberty. Low
doses of testosterone accelerate statural and craniofacial growth, particularly
in the delayed components, thus leading towards a normalization of facial
dimensions." (Verdonck et al., 1999). Osteoporosis in vertebrae, the diaphysis
of the radius, and neck of the femur in male leprosy patients were
"significantly correlated with [reduced] FT [free testosterone] in all three
regions of the skeleton." (Ishikama et al., 1999). Assuming sufficient DHEA is
available, too much testosterone increases bone size and prognathism; too little
has the opposite effect.
Continued cycling of cold during the upper Pleistocene and changes in
containment areas selected for hominids with different ratios of DHEA and
testosterone. Some combination of testosterone and DHEA occurred that favored
increased use of DHEA for brain growth. A change in the ratio of DHEA and
testosterone can slow the onset of puberty and increase anterior brain size.
Producing less DHEA reduces the effects of testosterone. Reduced containment
(testosterone) or reduced nutrition will slow the pace of puberty. (Increased
nutrition should favor those with early puberty.) The percentage of high
testosterone individuals would decrease and average size of the forebrain would
increase. This began in H. antecessor and H. heidelbergensis. Delayed puberty
and increased brain size produced Homo sapiens. Increased brain growth in H.
sapiens occurred in the anterior portion of the brain, the prefrontal lobes.
This produces the high forehead.
Another shift downward in testosterone levels in a population could occur
rapidly. Testosterone compromises the immune system. The effects are especially
dangerous when trauma is involved. "Male gender is associated with a
dramatically increased risk of major infections following trauma . This effect
is most significant following injuries of moderate severity and persists in all
age groups." (Offner et al., 1999). "Castration before soft-tissue trauma and
hemorrhagic shock maintains normal immune function in male mice, but
sham-castrated male mice show significant immunodepression. The maintenance of
immune function by androgen deficiency does not seem to be related to changes in
the release of corticosterone. We conclude that male sex steroids are involved
in the immunodepression observed in after trauma-hemorrhage. Thus, the use of
testosterone-blocking agents following trauma-hemorrhage should prevent the
depression of immune functions and decrease the susceptibility to sepsis under
those conditions." (Wiehmann et al., 1996). These negative effects of
testosterone on immunity could increase the probability of infectious epidemics
that could radically change the percentage of individuals of higher testosterone
in a population. This is very possibly the mechanism involved in extinctions of
the robust Australopithecines and various Homo populations.
Once a population is reduced in high testosterone individuals, a stable
population could exist for some time. However, due to the influence of
testosterone on reproduction, most populations will regain their high levels of
testosterone in time. Every positive increase in nutrition would increase the
probability of increasing the percentage of high testosterone individuals.
Therefore, a "cycling" of high testosterone populations should occur. This may
have occurred at the end of the Upper Paleolithic, through the Neolithic, when
body size in males and females clearly declined (Frayer, 1984). A reduction in
body size indicates that individuals of high testosterone levels in the
population died. Body size then increased into the Middle Ages during which
epidemics occurred with some frequency. Increased availability of food increases
the rate of these cycles, but does not cause them. People of high testosterone
simply reproduce faster when more food is available.
Homo sapiens exhibit a constellation of characteristics that separate sapiens
from other hominids. Postcranial skeleton, teeth, and craniofacial size are all
reduced coincidentally with changes in brain growth, that is, increases in size
in the frontal areas. Earlier, I suggested that canines are reduced in size in
Australopithecus because the brain is using DHEA for growth at the expense of
these teeth. The part of the brain that increased in Australopithecus reduced
growth of front teeth. These are increases mainly in the posterior parts of the
brain. Posterior growth of the brain retards growth of anterior teeth because
they occur concurrently. Many hominids exhibit increased posterior brain size
and reduced anterior teeth. The increase in brain growth of Homo sapiens
includes the posterior and the anterior parts of the cerebrum. Therefore, in
Homo sapiens, both the anterior and posterior teeth compete for DHEA during
times of brain growth. This is why the entire dentition is reduced in Homo
sapiens.
There are two dentitions in humans. DHEA levels are very high at birth, then
decline to very low levels within a year and remain low for some time. Around
age five to six, DHEA levels increase rapidly (adrenarche) and peak around age
twenty, at levels about half as much as that of the levels at birth. The brain
is using so much DHEA for growth and development during early childhood that
measurable levels of DHEA are very low. From age twenty, DHEA levels begin to
decline, reaching very low levels in old age. The high levels of DHEA at birth
stimulate growth of deciduous teeth. This period of high levels of DHEA declines
rapidly to very low levels in the first year. This decline of DHEA of early
childhood is so low that it does not support continued maintenance of the
deciduous teeth, and they are lost. The permanent dentition occurs as a result
of increasing DHEA beginning at adrenarche. Adrenarche begins as the brain
begins to finalize growth. These teeth are supported until DHEA begins to
decline in old age, unless something interferes with DHEA. This explains human
dentition. This implies that teeth are very sensitive to DHEA levels. With the
simple assumption that the bone of the mandible is less sensitive to reduced
DHEA, the reduction of the size of the anterior teeth produces the chin.
Summary
Australopithecus and Homo evolved as consequence of differential gene
regulation, in continuous, relatively comparable genomes, resulting mainly from
chronological differences in production of the androgenic hormones, testosterone
and dehydroepiandrosterone (DHEA). The cold periods of the Pleistocene epoch
selected for individuals of higher DHEA, which interacted with levels of
testosterone that varied according to behavioral advantages. The two principal
events of hominid evolution are 1) increased testosterone in females, that
stimulated increased testosterone in males, and 2) the amplification of
testosterone-directed characteristics by increased DHEA. The effects of these
events resulted in bipedal, upright locomotion, breasts as sexual displays,
larger brains, and the effects of increased use of DHEA by larger brains
throughout the body.
Individuals who produce large amounts of testosterone are vulnerable to
infections. Moreover, high testosterone individuals may act as carriers of
infectious agents. Testosterone and puberty are directly connected to
"establishment and maintenance of the carrier state" of an infectious virus in
horses (McCollum et al., 1994; Holyoak et al., 1993). This may have caused past
epidemics, when populations were composed of high percentages of high
testosterone individuals in dense populations. The end result would be a new
population reduced in the testosterone to DHEA ratio. This may have produced the
first population of Homo sapiens and, thereafter, periodically reduced the
percentages of individuals of high testosterone in later populations.
Increased amounts of DHEA for relatively lengthy, slower development of the
brain results in larger brains in the remaining population. These types of
events increase during times of higher population density due to increased
nutrition. This phenomenon is identifiable as the decline in body size that
occurred from the upper Paleolithic through the Neolithic periods. That is,
increased food increases reproduction rates and concentrates high testosterone
individuals into population centers. When testosterone reaches supra-optimal
levels, infection rates increase. Body size increased in the Middle Ages, which
frequently included epidemics. Learning disabilities are "significantly
associated" with high testosterone levels (Kirkpatrick et al., 1993). The
Renaissance followed the Middle Ages. Populations will periodically cycle
through times of increased and reduced percentages of high testosterone
individuals. Civilizations evolve in this manner. I suggest the increase in
percentage of individuals of higher testosterone produces the "secular trend,"
in populations. The secular trend is real, identifiable, and vigorous in the
U.S.A., at this time (Freedman et al., 2000).
This is a new explanation of human evolution. It accounts for all aspects of
human evolution, including the formation and declines of Australopithecus and
Homo, formation and declines of civilization, and is identifiable in current
populations.
References
Bachrach, L.K., Hastie, T., Wang, M.C., Narasimhan, B., & Marcus, R. (1999).
Bone mineral acquisition in healthy Asian, Hispanic, black, and Caucasian youth:
a longitudinal study. J. Clin. Endocrinol. Metab. 84, 4702-12.
Baulieu, E.E. (1999). Neuroactive neurosteroids: dehydroepiandrosterone (DHEA)
and DHEA sulphate. Acta. Paediatr. Suppl. 88, 78-80.
Bobyleva, V., Kneer, N., Bellei, M., & Lardy, H.A. (1993). Concerning the
mechanism of increased thermogenesis in rats treated with
dehydroepiandrosterone. J. Bioenerg. Biomembr. 25, 313-21.
Clark, A.S. & Goldman-Rakic, P.S. (1989). Gonadal hormones influence the
emergence of cortical function in nonhuman primates. Behav. Neurosci. 103,
1287-95.
Crawford, B.A., Harewood, W.J. & Handelsman, D.J. (1997). Growth and hormone
characteristics of pubertal development in the hamadryas baboon. J. Med.
Primatol. 26, 153-63.
Davis S.R., McCloud, P., Strauss, B.J. & Burger, H. (1995). Testosterone
enhances estradiol's effects on postmenopausal bone density and sexuality.
Maturitas 21, 227-36.
Davis, S.R. (1998). The clinical use of androgens in female sexual disorders. J.
Sex. Marital Ther. 24, 153-63.
Frayer, D.W. (1984). Biological and cultural change in the european late
pleistocene and early holocene. In (Smith, F. H. & Spencer, F., Eds.) The
Origins of Modern Humans. A World Survey of the Fossil Evidence, New York, Alan
R. Liss, Inc., pages 211-50.
Freedman, D.S., Khan, L.K., Serdula, M.K., Srinivasan, S.R., & Berenson, G.S.
(2000). Secular Trends in Height Among Children During 2 Decades. The Bogalusa
Heart Study. Arch. Pediatr. Adolesc. Med. 154, 155-61.
Gasperino, J. (1995). Androgenic regulation of bone mass in women. A review.
Clin. Orthop. 311, 278-86.
Gray, H. (1966). Anatomy of the Human Body, (Goss, C.M., Ed.). Philadelphia, Lea
& Fegiber, page 500.
Hobson, W., Coulston, F., Faiman, C., Winter, J.S. & Reyes, F. (1976).
Reproductive endocrinology of female chimpanzees: a suitable model of humans. J.
Toxicol. Environ. Health 1, 657-68.
Holyoak, G.R., Little, T.V., McCollam, W. H., & Timoney, P.J. (1993).
Relationship between onset of puberty and establishment of persistent infection
with equine arteritis virus in the experimentally infected colt. J. Comp.
Pathol.109, 29-46.
Iguchi, T., Irisawa, S., Fukazawa, Y., Uesugi, Y. & Takasugi, N. (1989).
Morphometric analysis of the development of sexual dimorphism of the mouse
pelvis. Anat. Rec. 224, 490-4.
Ishikawa, S., Ishikawa, A., Yoh, K., Tanaka, H.. & Fujiwara, M. (1999).
Osteoporosis in male and female leprosy patients. Calcif. Tissue Int. 64, 144-7.
Kalloo N.B., Gearhart J.P., & Barrack E.R. (1993). Sexually dimorphic expression
of estrogen receptors, but not of androgen receptors in human fetal external
genitalia. J. Clin. Endocrinol. Metab. 77, 692-8.
Kaplan, H.S. & Owett, T. (1993). The female androgen deficiency syndrome. J.
Sex. Marital Ther. 19, 3-24.
Kasperk, C H., Wakley, G.K., Hierl, T., & Ziegler, R. (1997). Gonadal and
adrenal androgens are potent regulators of human bone cell metabolism in vitro.
J. Bone Miner. Res. 12, 464-71.
Kirkpatrick, S.W., Campbell, P.S., Wharry, R.E. & Robinson, S.L. (1993).
Salivary testosterone in children with and without learning disabilities.
Physiol. Behav. 53, 583-6.
Kondo, S., Hozumi, Y. & Aso, K. (1990). Organ culture of human scalp hair
follicles: effect of testosterone and oestrogen on hair growth. Arch. Dermatol.
Res. 282, 442-5.
Labrie, F., Diamond, P., Cusan, L., Gomez, J.L., Belanger, A., & Candas, B.
(1997). Effect of 12-month dehydroepiandrosterone replacement therapy on bone,
vagina, and endometrium in postmenopausal women. J. Clin. Endocrinol. Metab. 82,
3498-505.
Lieberman, L.S. (1982). Normal and abnormal sexual dimorphic patterns of growth
and development. In (R.L. Hall, Ed.) Sexual Dimorphism in Homo Sapiens A
Question of Size, New York: Praeger, page 281.
Likitmaskul, S., Cowell, C.T., Donaghue, K., Kreutzmann, D.J., Howard, N.J.,
Blades, B., & Silink, M. (1995). 'Exaggerated adrenarche' in children presenting
with premature adrenarche. Clin. Endocrinol. (Oxf). 42, 265-72.
Martel, C., Sourla, A., Pelletier, G., Labrie, C., Fournier, M., Picard, S., Li,
S., Stojanovic, M., & Labrie, F. (1998). Predominant androgenic component in the
stimulatory effect of dehydroepiandrosterone on bone mineral density in the rat.
J. Endocinol. 157, 433-42.
McCollum, W.H., Little, T.V., Timoney, P.J., & Swerczek, T.W. (1994). Resistance
of castrated male horses to attempted establishment of the carrier state with
equine arteritis virus. J. Comp.Pathol.111, 383-8.
Meusy-Dessolle, N. & Dang, D.C. (1985). Plasma concentrations of testosterone,
dihydrotestosterone, delta 4-androstenedione, dehydroepiandrosterone and
oestradiol-17 beta in the crab-eating monkey (Macaca fascicularis) from birth to
adulthood. J. Reprod. Fertil. 74, 347-59.
Nadler, R.D. (1980). Reproductive physiology and behaviour of gorillas. J.
Reprod. Fertil. Suppl. 28, 79-89.
Nadler, R.D., Dahl, J.F. & Collins, D.C. (1993). Serum and urinary
concentrations of sex hormones and genital swelling during the menstrual cycle
of the gibbon. J. Endocrinol. 136, 447-55.
Nimrod, A. & Ryan, K.J. (1975). Aromatization of androgens by human abdominal
and breast fat tissue. J. Clin. Endocrinol. Metab. 40, 367-72.
Offner, P.J., Moore, E.E. & Biffl, W.L. (1999). Male gender is a risk factor for
major infections after surgery. Arch. Surg. 134, 935-8.
Ozasa, H. & Gould, K.G. (1982). Demonstration and characterization of estrogen
receptor in chimpanzee sex skin: correlation between nuclear receptor levels and
degree of swelling. Endocrinology 111, 125-31.
Perel, E., Davis, S. & Killinger, D.W. (1981). Androgen metabolism in male and
female breast tissue. Steroids 37, 345-52.
Perry, H.M., 3rd., Horowitz, M., Morley, J.E., Fleming, S., Jensen, J.,
Caccione, P., Miller, D.K., Kaiser, F.E., & Sundarum, M. (1996). Aging and bone
metabolism in African American and Caucasian women. J. Clin. Endocrinol. Metab.
81, 1108-17.
Ross, R., Bernstein, L., Judd, H., Hanisch, R., Pike, M., & Henderson, B.
(1986). Serum testosterone levels in healthy young black and white men. J. Natl.
Cancer Inst. 76, 45-8.
Sarrel, P., Dobay B.J., & Wiita, B. (1998). Estrogen and estrogen-androgen
replacement in postmenopausal women dissatisfied with estrogen-only therapy.
Sexual behavior and neuroendocrine responses. Reprod. Med. 43, 847-56.
Tagliaferro, A.R., Davis, J.R., Truchon, S., & Van Hamont, N. (1986). Effects of
dehydroepiandrosterone acetate on metabolism, body weight and composition of
male and female rats. J. Nutr. 116, 1977-83.
Tuiten A., Van Honk J., Koppeschaar, H., Bernaards C., & Verbaten, R. (2000).
Time course of effects of testosterone administration on sexual arousal in
women. Arch. Gen. Psychiatry 57, 149-53.
Verdonck, A. Gaethofs, M., Carels, C., & de Zegher, F. (1999). Effect of
low-dose testosterone treatment on craniofacial growth in boys with delayed
puberty. Eur. J. Orthod. 21, 137-43.
Wickings, E.J. & Nieschlag, E. (1980). Seasonality in endocrine and exocrine
testicular function of the adult rhesus monkey (Macaca mulatta). Int. J. Androl.
3, 87-104.
Wiehmann, M.W., Zellweger, R., DeMaso, C.M., Ayala, A. & Chaudry, I.H. (1996).
Mechanism of immunosuppression in males following trauma-hemorrhage. Critical
role of testosterone. Arch. Surg. 131, 1186-91.
Wilson, M.I. (1977). A note on the external genitalia of female squirrel monkeys
(Saimiri sciureus). J. Med. Primatol. 6, 181-5.
Winter, J.S.D., Faiman, C., Hobson, W.C. & Reyes, F.I. (1980). The endocrine
basis of sexual development in the chimpanzee. In (R.V. Short & B.J. Weir, Eds.)
The Great Apes of Africa, Text-fig. 2 (testosterone, males), page 134, Text-fig.
5 (testosterone, females), page 137, and Text-fig. 3, page 135, (estradiol,
females). J. Reprod. Fertil. Suppl. 28.
Zingeser, M.R. & Phoenix, C.H. (1978). Metric characteristics of the canine
dental complex in prenatally androgenized female rhesus monkeys (Macaca
mulatta). Am. J. Phys. Anthropol. 49, 187-92.
