Kisspeptin and Puberty in Mammals - Kisspeptin Signaling in Reproductive Biology - page 249

GnRH and/or gonadotropin has been described in many mammalian species, includ-
ing humans (see [ 16 - 20 ]). In males, an increase in pulsatile GnRH release at puberty
activates tonic gonadotropin secretion that, in turn, results in the onset of elevated
levels of testicular testosterone secretion, which in combination with FSH, initiates
spermatogenesis. Tonic LH secretion is composed of intermittent secretory epi-
sodes of the hormone, which refl ect a corresponding pattern of pulsatile GnRH
release by the hypothalamus [ 21 ]. In females, an increase in pulsatile GnRH release
also drives tonic gonadotropin secretion, which is responsible for folliculogenesis
and estradiol (E 2 ) secretion. Ovulation in most mammalian species, however, also
requires development of the capacity to induce a large surge of GnRH in response
to the positive feedback action of the rising circulating E 2 levels secreted by the
follicle(s) destined to ovulate at mid cycle [ 22 ]. Currently, the mechanism for these
two modes of GnRH release (pulsatile vs. surge) is unclear.
There are two basic developmental patterns of pulsatile GnRH release from
birth until the onset of puberty. In highly evolved primates, such as man and
macaques, GnRH pulsatility is robust during the infantile period after birth, but is
subsequently dampened during juvenile development (and childhood in humans),
resulting in a hypogonadotropic state and relative quiescence of the gonad [ 18 , 20 ].
The hiatus in pulsatile GnRH release during the juvenile period may be viewed as
a consequence of a neurobiological “brake” that holds GnRH release in check until
the initiation of the onset of puberty [ 15 ]. It is important to note that this is a con-
ceptual brake and may be accounted for by either the imposition of an inhibitory
input and/or the loss of a stimulatory input to GnRH neurons [ 18 ]. Our current
viewpoint is that this conceptual brake is an inhibitory neurocircuit in the brain [ 17 ].
The juvenile phase of primate development is terminated by release from the
brake, leading to a reactivation of robust GnRH pulsatility [ 15 ]. Because this
juvenile restraint on pulsatile GnRH release is observed in neonatally castrated
monkeys [ 23 , 24 ] and in agonadal humans [ 25 , 26 ], and because low levels of LH
and GnRH release during the juvenile period in ovariectomized female monkeys
are not further suppressed by ovarian steroids [ 27 ], the hiatus of pulsatile GnRH
release during the juvenile period of primate development is independent of ovarian
or testicular steroids.
This control system may be contrasted to that in non-primate species, in which
LH release (and presumably GnRH release) immediately after birth is minimal but
increases before the onset of puberty, with the prepubertal gonad playing a critical
role in restraining GnRH release prior to puberty. For example, in sheep and rodents,
gonadotropin secretion (and presumably GnRH release) is suppressed by small
amounts of gonadal steroid after birth through the juvenile period, but at a time prior
to puberty, low levels of steroids are no longer inhibitory [ 19 , 28 ]. Moreover, neo-
natal gonadectomy in sheep, rats, and guinea pigs increases LH levels, and in sheep
and rats, administration of gonadal steroids suppresses LH levels [ 29 , 30 ]. Therefore,
the control system governing reactivation of GnRH release at puberty in primates is
different from that regulating the postnatal development of pulsatile GnRH release
in non-primates.