The overall goal of this continuing research is to delineate the mechanisms involved in the suppression of gonadotropin secretion induced by the suckling stimulus. All of our data is consistent with the hypothesis that suckling greatly suppresses GnRH release from the hypothalamus leading to a decrease in pituitary gonadotropin function, as evidenced by a decrease in pituitary GnRH receptors, pituitary sensitivity to GnRH, LH submit mRNA and pulsatile LH secretion. Thus, this system provides an excellent model in which to study the mechanisms involved in the restoration of normal pituitary gonadotrope function from a physiologically suppressed state. The studies proposed will also attempt to identify the factors associated with lactation that are responsible for the suppression of GnRH secretion. The proposed experiments will examine the differential regulation of LH and FSH secretion by measuring LH and FSH subunit mRNA levels during lactation and after pup removal, and also will examine the effects of administration of pulsatile GnRH and estradiol and progesterone on gonadotrophin subunit mRNA levels. Studies will determine if factors other than suppressed GnRH secretion may play a role during lactation in the decrease in pituitary GnRH receptors and pituitary sensitivity to GnRH. Studies will also more clearly define the recovery process of GnRH secretion after pup removal by characterizing the pattern of LH secretion between 0 and 24hr after pup removal and will test the hypothesis that the pattern of GnRH recovery after pup removal consists of an early increase in basal secretion, which upregulates GnRH receptors, followed later by the superimposition of GnRH pulses, which initiates pulsatile LH secretion. Techniques will be developed to measure GnRH biosynthesis by using 3H-amino acids to label newly synthesized GnRH. It is hoped that changes in GnRH biosynthesis will serve as an indicator of changes in GnRH neuronal activity. Studies will determine whether factors involved in suckling-induced prolactin and oxytocin secretion, such as VIP, oxytocin, activin, and serotonin, may also mediate the suppression of GnRH secretion. Because our experiments have shown that suppression of GnRH secretion requires input from areas of the CNS outside the hypothalamus, and neural impulses from the suckling stimulus travel through the lower brainstem to reach the hypothalamus, experiments will be conducted to identify areas in the lower brainstem which are responsible for the inhibitory input which suppress GnRH secretion. These studies should provide new insights into the regulation of GnRH secretion and pituitary gonadotrope function, and thus may contribute to new approaches for contraception, to correct infertility problems, and to an understanding of the mechanisms participating in lactation amenorrhea.
Showing the most recent 10 out of 91 publications
