LACTATIONAL AMENORRHEA

Postpartum lactation in humans and monkeys is associated with ovarian
quiescence attributed to suckling-induced deficits in GnRH secretion and
hyperprolactinemia. The work proposed in this application would
investigate the validity and nature of these mechanisms in the rhesus
monkey, a primate in which the control of gonadotropin secretion and
ovarian function appear similar to the human. 1. Because a reduced frequency of pulsatile GnRH release has the potential
of disrupting normal gonadotropin secretion and ovarian cycles, the
intermittent discharge of this hypothalamic hormone will be assessed
indirectly by measuring pulsatile LH release in chronically catheterized
monkeys nursing their infants. Moreover, changes in pulsatile LH release
that might occur following abrupt removal of the infant will be recorded at
several postpartum intervals. To relate the intensity of the suckling
stimulus to the duration of gonadotropin suppression during lactation, some
rhesus infants will be retricted to mother's milk during the usual period
of weaning in an attempt to delay resumption of maternal pituitary function
as assessed by pulsatile LH secretion and the positive feedback action of
estradiol. 2. The possibility that the sensitivity of the hypothalamic-pituitary axis
to the negative feedback action of estrogen is enhanced during lactation
will be tested in ovariectomized monkeys bearing estradiol capsules that
produce low circulating levels of the steroid. 3. Exogenous pulses of GnRH will be administered to nursing monkeys in an
attempt to re-initiate pituitary and ovarian function. Moreover, the
possible role of progesterone in mediating the inhibitory action of
lactational hyperprolactinemia on ovarian follicular development will be
investigated in monkeys with hypothalamic lesions receiving pulsatile GnRH
replacement and progesterone capsules. 4. The central neural mechanisms underlying the inhibition of GnRH
secretion in lactating monkeys will be studied by measuring pulsatile LH
release during suckling following administration of antagonists to the
endogenous opioid peptides, dopamine, and serotonin. These studies, which are difficult to perform under suitable controlled
conditions in humans, will serve to delineate the mechanisms involved in
lactational amenorrhea in a primate model.