Biomedical Engineering Reference
In-Depth Information
marmoset, Callithrix jacchus; Bolivian squirrel monkey,
Saimiri boliviensis; Ma's owl monkey, Aotus nancymaee),
the pituitary secretes chorionic gonadotropin (CG) instead
of LH. Correspondingly, the gonads in some or all New
World monkeys express a modified form of the LH receptor
in which exon 10 is not expressed and which is activated
selectively by CG (
Gromoll et al., 2003; M¨ ller et al.,
2004a,b; Scammell et al., 2008
).
The major function of LH in males is stimulation of
androgen release by the Leydig cells. The testis of the
rhesus monkey responds rapidly to LH; increased concen-
trations of serum testosterone (T) are evident within
30 minutes, with maximum concentrations achieved by
1 hour (
Toivola et al., 1978; Wickings and Nieschlag,
1980a,b
). Administration of human CG (hCG; a molecule
with analogous functions to LH) for a 3-day duration
results in a 10-fold increase in serum T concentrations in
the adult rhesus macaque (
Wickings et al., 1986
). Treat-
ment of adult cynomolgus (or long-tailed) macaques
(Macaca fasicularis) with hCG for 16 days results in
a 163% increase in the number of Leydig cells and a nine-
fold rise in plasma T concentration (
Teerds, et al., 1989
).
Correspondingly, T is an important regulator of LH secre-
tion, exerting negative feedback to reduce the frequency of
LH and presumably GnRH pulses (reviewed by
Tilbrook
and Clarker, 2001
). The T-mediated feedback in nonhuman
primates occurs primarily through brain cell populations,
although not through direct effects on GnRH neurons that
appear to lack receptors for the sex steroids
e
androgens,
estrogens, and progesterone (
Saltzman et al., 2011
).
In contrast to LH, the major functions of FSH in males
involve development of the gonads, especially production
of Leydig cells, and regulation of spermatogenesis, the
latter being mediated through actions on Sertoli cells.
Whereas LH release is highly sensitive to GnRH pulse
frequency, FSH release is not, so that changes in GnRH
pulse frequency alter the ratio of circulating FSH to LH
(
Zeleznik and Pohl, 2006
). The major testicular hormones
controlling FSH secretion are inhibin B and activins, two
glycoprotein hormones produced by the Sertoli cells that
inhibit and stimulate, respectively, pituitary release of FSH
(
McLachlan et al., 2002
).
The ovarian cycle in nonhuman primates, as in other
species, is governed by a complex interplay among the
gonads, the gonadotropes in the anterior pituitary, and the
GnRH pulse generator in the medial basal hypothalamus
(reviewed by
Johnson and Everitt, 2000; Messinis, 2006;
Zeleznik and Pohl, 2006
). During the follicular phase, LH
and FSH are released in low-amplitude, circhoral pulses,
reflecting negative-feedback effects of estrogens on pulse
amplitude but not frequency. At midcycle, estrogens trigger
positive-feedback surges in GnRH, LH, and FSH, eliciting
increases in pulse frequency and/or amplitude. Fully
developed gonadotropin surges in women require the
presence of small amounts of progesterone (P
4
); however,
no such effect is seen in rhesus macaques (
Zeleznik and
Pohl, 2006
). The luteal phase, following ovulation, is
characterized by low-frequency, high-amplitude LH pulses,
reflecting negative feedback primarily by P
4
. In addition to
ovarian steroids, inhibins secreted by granulosa and luteal
cells possibly exert negative feedback specifically on FSH
release; however, the precise role of inhibins in nonhuman
primate ovarian cycles is not yet clear (
Zeleznik and Pohl,
2006; Randolph, 2008
). Interestingly, FSH concentrations
are elevated during the luteal phase in squirrel monkeys,
suggesting that development of antral follicles may occur
during this period, possibly permitting the extremely short
(~5-day) follicular phase of these species (
Yeoman et al.,
2000
).
Estrogens generate both negative and positive feedback
effects on gonadotropin release. Negative feedback effects
occur at both the level of the hypothalamus and the pitui-
tary (
Mizuno and Terasawa, 2005
). A variety of experi-
mental approaches have suggested that positive feedback
by estrogens at the pituitary alone is sufficient to generate
preovulatory LH surges, although GnRH plays an obligate
permissive role. Nonetheless, other studies have indicated
that hypothalamic release of GnRH increases in response to
sustained elevations of estrogens. Negative feedback
effects of P
4
on GTH pulse frequency are assumed to occur
at least partly within the central nervous system and are
mediated at least in part by endogenous opioids. In addi-
tion, negative feedback effects of both estrogens and P
4
at
the level of the brain appear to be mediated in part by
kisspeptin (Kp) (
Plant et al., 2009
).
Puberty
Puberty is the period of development during which the
individual achieves the capacity to reproduce successfully.
This period is characterized by morphological, physio-
logical, and behavioral changes driven by maturation
and activation of the hypothalamic-pituitary-gonadal
(HPG) axis (i.e. gonadarche) and in some species, of the
hypothalamus-pituitary-adrenal (HPA) axis (i.e. adre-
narche). An excellent review of puberty in nonhuman
primates can be found in
Plant and Witchel (2006)
.
In infant nonhuman primates, the pituitary and gonads
secrete high levels of GTHs (i.e. LH and FSH) and steroid
hormones (e.g. T, dihydrotestosterone (DHT), estrone (E
1
),
and (E
2
)), respectively, for a period of weeks to months.
This period of neonatal gonadal activity ends with the onset
of the so-called juvenile or prepubertal hiatus, during which
gonadotropin levels drop precipitously and the gonads enter
a dormant state, especially in males (reviewed by
Plant and
Witchel, 2006
). Gonadal “re-awakening” occurs at the time
of gonadarche.
