Biomedical Engineering Reference
In-Depth Information
In females, the surge in gonadotropins stimulates the
initiation of cyclical ovarian activity (i.e. folliculogenesis)
leading to development of follicles capable of ovulation. In
concert, the pituitary gonadotropes develop the capacity for
positive feedback response to estrogens, leading to the first
ovulation. In rhesus macaques, menarche (the first
menstrual period) precedes by approximately a year the
onset of regular, fertile ovulatory cycles, with the initial
cycles being frequently anovulatory and irregular (
Dixson,
1998; Saltzman et al., 2011
). Increasing estrogen concen-
trations during the menarche stimulate uterine growth and
development of secondary sexual characteristics such as
coloration of sexual skin (
Dixson 1998
).
In males, body weight changes, testicular size and
position, presence of an ejaculate, elevations in T, and
conception are all aspects of attainment of sexual maturity.
Gonadarche in male nonhuman primates is characterized
by dramatic elevations in circulating concentrations of LH
and to a lesser extent, FSH, reflecting primarily an increase
in secretory pulse amplitude. These GTH increases, which
are thought to reflect a concomitant amplification of
pulsatile GnRH release from the hypothalamus, stimulate
an increase in testicular volume (associated with growth of
the seminiferous tubules, maturation of Sertoli cells, and
proliferation of germ cells), development of Leydig cells,
secretion of high levels of gonadal androgens, and initiation
of spermatogenesis (
Plant and Witchel, 2006
). The primary
androgen formed by the testis is T, which is responsible for
the normal development of male structures, including
secondary sexual characteristics such as facial and genital
coloration (e.g. mandrill, Mandrillus sphinx) and special-
ized facial or body hair (e.g. baboon, Papio hamadryas
hamadryas) as well as sexual behavior (
Dixson, 1998
).
Testosterone may also be responsible for programming
regions in the central nervous system (CNS) that regulate
testicular function and male behavior. Normal differentia-
tion requires the presence of T, but the prostate and external
genitalia
release during puberty and adulthood (
Plant and Witchel,
2006
).
Recent attention has focused on the role of the neuro-
peptide Kp and its receptor, GPR54 (also known as
KiSS1R), in regulating gonadarche in humans and other
primates (
Plant, et al. 2009
). Specifically, Kp-GPR54
signaling has been implicated in the control of hypotha-
lamic GnRH release, pituitary GTH release, and onset of
puberty in a number of mammalian species,
including
rhesus macaques (
Roa et al., 2008
).
The factors that determine the timing of these processes
remain poorly understood (reviewed by
Plant and Witchel,
2006
) but are clearly multifactorial, involving genetic,
physiological, and environmental influences. An early
hypothesis
e
that the timing of puberty is governed by an
endogenous “pubertal clock” in the CNS that initiates
puberty at a specific age
e
is not widely accepted. Instead,
the timing of puberty has long been thought to be governed
by a putative “somatometer” that measures some index of
somatic growth. The somatometer hypothesis is supported
by compelling evidence. It has been noted that dietary
restriction can result in a decline in both body weight and
circulating gonadotropins when food intake is reduced in
castrated males (
Dubey et al., 1986
). The observed
decreases in FSH and LH were, however, restored by an
infusion of GnRH. It has been suggested that insulin or
amino acids could provide the link between nutritional
status and reproductive function by influencing the
synthesis of neurotransmitters critical for maintaining
GnRH secretion (
Steiner et al., 1983
). Studies with
M. fascicularis have shown that long-term administration
of amino acids and glucose stimulates adult-like LH/FSH,
presumably through the release of GnRH (
Cameron et al.,
1985a,b
). It was concluded that blood-borne metabolic cues
that specifically sustain glucose-induced elevation of
insulin can stimulate the activity of GnRH-secreting cells
and that these factors may be responsible for mediating
maturational events within the brain (
Cameron et al.,
1985a,b
).
The index of somatic development being monitored is
not yet known. In recent years, attention has focused on
a possible role of the adipocyte-produced hormone leptin,
circulating concentrations of which correlate with body fat
mass. Findings in humans and rhesus macaques as well as
rodents suggest that leptin plays a critical, permissive role
in the onset of gonadarche (
Ebling, 2005; Plant and
Witchel, 2006; Kaplowitz, 2008
). Other indices of somatic
development that have been implicated in determining the
timing of puberty include insulin, growth hormone (GH),
ghrelin, and metabolic fuels (
Plant and Witchel, 2006;
Kaplowitz, 2008; Tena-Sempere, 2008
). Strenuous exer-
cise, undernutrition, and chronic disease can all delay the
onset of puberty, possibly acting through the putative
somatometer (
Plant and Witchel, 2006
).
require DHT for
appropriate development
(
Wilson et al., 1970
).
The proximate trigger for gonadarche involves matu-
ration of neural inputs to the GnRH neurons, eliciting the
dramatic increase in pulsatile GnRH secretion and,
consequently, increases in pituitary secretion of GTHs and
stimulation of gonadal endocrine and gametogenic
activity.
Studies in rhesus macaques have implicated several
neurotransmitters and neuropeptides in the onset of gona-
darche. These include the inhibitory neurotransmitter
GABA, which plays a key role in restraining GnRH
secretion during the juvenile period but exerts only modest
inhibitory effects on GnRH release after the onset of
puberty (
Terasawa, 2005
), and NPY, which has been
implicated both in inhibiting GnRH release during the
prepubertal hiatus and, paradoxically, in stimulating GnRH
