Male prenatal development Testes formation During mammalian development, the gonads are at first capable of becoming either
ovaries or testes. In humans, starting at about week 4, the gonadal rudiments are present within the
intermediate mesoderm adjacent to the developing kidneys. At about week 6, epithelial
sex cords develop within the forming testes and incorporate the
germ cells as they migrate into the gonads. In males, certain
Y chromosome genes, particularly
SRY, control development of the male phenotype, including conversion of the early bipotential gonad into testes. In males, the sex cords fully invade the developing gonads.
Androgen production The mesoderm-derived
epithelial cells of the sex cords in developing testes become the
Sertoli cells, which will function to support sperm cell formation. A minor population of nonepithelial cells appear between the tubules by week 8 of human fetal development. These are
Leydig cells. Soon after they differentiate, Leydig cells begin to produce androgens.
Androgen effects The androgens function as
paracrine hormones required by the Sertoli cells to support sperm production. They are also required for the masculinization of the developing male fetus (including penis and scrotum formation). Under the influence of androgens, remnants of the
mesonephron, the
Wolffian ducts, develop into the
epididymis,
vas deferens and
seminal vesicles. This action of androgens is supported by a hormone from Sertoli cells, Müllerian inhibitory hormone (MIH), which prevents the embryonic Müllerian ducts from developing into fallopian tubes and other female reproductive tract tissues in male embryos. MIH and androgens cooperate to allow for movement of testes into the scrotum.
Early regulation Before the production of the pituitary hormone
luteinizing hormone (LH) by the embryo starting at about weeks 11–12,
human chorionic gonadotrophin (hCG) promotes the differentiation of Leydig cells and their production of androgens at week 8. Androgen action in target tissues often involves conversion of testosterone to 5α-
dihydrotestosterone (DHT).
Male pubertal development At the time of
puberty, androgen levels increase dramatically in males, and androgens mediate the development of masculine
secondary sexual characteristics as well as the activation of
spermatogenesis and
fertility and masculine behavioral changes such as increased
sex drive. Masculine secondary sexual characteristics include
androgenic hair,
voice deepening, emergence of the
Adam's apple, broadening of the shoulders, increased
muscle mass, and
penile growth.
Spermatogenesis During puberty, androgen, LH and
follicle stimulating hormone (FSH) production increase and the sex cords hollow out, forming the seminiferous tubules, and the germ cells start to differentiate into sperm. Throughout adulthood, androgens and FSH cooperatively act on Sertoli cells in the testes to support sperm production. Exogenous androgen supplements can be used as a
male contraceptive. Elevated androgen levels caused by use of androgen supplements can inhibit production of LH and block production of endogenous androgens by Leydig cells. Without the locally high levels of androgens in testes due to androgen production by Leydig cells, the seminiferous tubules can degenerate, resulting in infertility. For this reason, many transdermal androgen patches are applied to the scrotum.
Fat deposition Males typically have less body fat than females. Recent results indicate androgens inhibit the ability of some fat cells to store lipids by blocking a signal transduction pathway that normally supports adipocyte function. Also, androgens, but not estrogens, increase beta
adrenergic receptors while decreasing alpha adrenergic receptors—which results in increased levels of epinephrine/norepinephrine due to lack of alpha-2 receptor negative feedback and decreased fat accumulation due to epinephrine/norepinephrine then acting on lipolysis-inducing beta receptors.
Muscle mass Males typically have more
skeletal muscle mass than females. Androgens promote the enlargement of skeletal muscle cells in a coordinated manner by acting on several cell types in skeletal muscle tissue. One cell type, called the
myoblast, conveys androgen receptors for generating muscle. Fusion of myoblasts generates
myotubes, in a process linked to androgen receptor levels. Higher androgen levels lead to increased expression of
androgen receptor.
Brain Circulating levels of androgens can influence human behavior because some
neurons are sensitive to steroid hormones. Androgen levels have been implicated in the regulation of human
aggression and libido. Indeed, androgens are capable of altering the structure of the brain in several species, including mice, rats, and primates, producing
sex differences. More recent studies showing the general
mood of
transgender men, who have undergone
transgender hormone replacement therapy replacing
estrogens with androgens, do not show any substantial long-term
behavioral changes. Numerous reports have shown androgens alone are capable of altering the
structure of the brain, but identification of which alterations in neuroanatomy stem from androgens or estrogens is difficult, because of their potential for conversion. Evidence from
neurogenesis (formation of new neurons) studies on male rats has shown that the
hippocampus is a useful brain region to examine when determining the effects of androgens on behavior. To examine
neurogenesis, wild-type male rats were compared with male rats that had
androgen insensitivity syndrome, a genetic difference resulting in complete or partial insensitivity to androgens and a lack of external
male genitalia. Neural injections of
bromodeoxyuridine (BrdU) were applied to males of both groups to test for
neurogenesis. Analysis showed that
testosterone and
dihydrotestosterone regulated adult
hippocampal neurogenesis (AHN). Adult hippocampal neurogenesis was regulated through the
androgen receptor in the wild-type male rats, but not in the TMF male rats. To further test the role of activated androgen receptors on AHN,
flutamide, an
antiandrogen drug that competes with testosterone and dihydrotestosterone for androgen receptors, and dihydrotestosterone were administered to normal male rats. Dihydrotestosterone increased the number of BrdU cells, while flutamide inhibited these cells. Moreover, estrogens had no effect. This research demonstrates how androgens can increase AHN. Researchers also examined how mild exercise affected androgen synthesis which in turn causes AHN activation of
N-methyl--aspartate (NMDA) receptors.
NMDA induces a calcium flux that allows for synaptic plasticity which is crucial for AHN. Researchers injected both orchidectomized (ORX) (castrated) and sham castrated male rats with
BrdU to determine if the number of new cells was increased. They found that AHN in male rats is increased with mild exercise by boosting synthesis of
dihydrotestosterone in the
hippocampus. Again it was noted that AHN was not increased via activation of the
estrogen receptors. Androgen regulation decreases the likelihood of
depression in males. In
preadolescent male rats,
neonatal rats treated with
flutamide developed more
depression-like symptoms compared to control rats. Again
BrdU was injected into both groups of rats in order to see if cells were multiplying in the living tissue. These results demonstrate how the organization of androgens has a positive effect on
preadolescent hippocampal neurogenesis that may be linked with lower
depression-like symptoms.
Social isolation has a hindering effect in AHN whereas normal regulation of androgens increases AHN. A study using male rats showed that
testosterone may block
social isolation, which results in
hippocampal neurogenesis reaching
homeostasis—regulation that keeps internal conditions stable. A
Brdu analysis showed that excess
testosterone did not increase this blocking effect against
social isolation; that is, the natural circulating levels of androgens cancel out the negative effects of
social isolation on AHN.
Female-specific effects Androgens have potential roles in relaxation of the
myometrium via non-genomic,
androgen receptor-independent pathways, preventing premature
uterine contractions in pregnancy.
Androgen insensitivity Reduced ability of an
XY-
karyotype fetus to respond to androgens can result in one of several conditions, including infertility and several forms of
intersex conditions.
Miscellaneous Yolk androgen levels in certain birds have been positively correlated to social dominance later in life. See
American coot. ==Biological activity==