Biology Reference
In-Depth Information
lengthening of the free-running period), resulted in a lengthening of the ovulatory
cycle to precisely four times the period of an individual's circadian rhythm,
establishing that the ovulatory cycle and locomotor rhythms are governed by a com-
parable endogenous timing system [
35
]. Because estrous and activity onset were
coupled temporally, it was suggested that the LH surge and locomotor activity are
controlled by either a single, endogenous oscillator or a coupled, multioscillator
system that regulates the rhythms of each process independently [
35
]. The former
hypothesis postulated that the reproductive axis “tracks” four circadian cycles and
ovulation occurs after the count is complete.
Converging lines of evidence over the next three decades established that both of
these hypotheses are partially correct. We now know that the SCN provides a daily,
stimulatory signal to the reproductive axis each day of the estrous cycle, closely
preceding the active phase, in most spontaneously ovulating rodents [
5
,
36
,
37
],
indicating that a single clock subserves both processes. However, this signal is only
effective at stimulating the GnRH system to produce the LH surge in the presence
of estradiol concentrations above a critical threshold. Prior to the day of proestrus,
the developing ovarian follicles secrete insuffi cient estradiol to fulfi ll this criterion.
The nature of the daily stimulatory signal from the SCN can be unmasked by
implanting animals with estradiol capsules that result in proestrus concentrations of
this hormone; in this case, daily LH surges occur [
37
-
39
]. Regarding the second
hypothesis suggesting a multioscillator organization, although distinct clocks do not
underlie locomotor rhythms and estrus, a hierarchical clock structure exists in which
the SCN acts as the master pacemaker coordinating rhythmicity in subordinate
oscillator systems of the reproductive axis, an arrangement discussed further below.
Sex Steroid and Circadian Integration in Ovulatory Control
Through negative-feedback effects of sex steroids, LH is maintained at low concen-
trations throughout most of the ovulatory cycle, paradoxically, high concentrations of
estradiol are required for the SCN to trigger ovulation (i.e., positive feedback) [
5
,
36
,
37
,
40
]. The site(s) of integration for positive and negative-feedback effects of estra-
diol with the circadian timing system are complex and not fully understood. As
described below, current evidence indicates that one important site of integration for
the positive feedback effects of estradiol with circadian signaling is the kisspeptin
network in the anteroventral periventricular nucleus (AVPV).
Circadian Neurochemical Communication and Ovulation
Despite the fact that the SCN is crucial for both locomotor behavior and the initiation
of ovulation, each process is likely mediated by distinct communication modalities.
In arrhythmic, SCN-lesioned hamsters, fetal SCN transplants restore locomotor,
Search WWH ::
Custom Search