The medial basal hypothalamus secretes GnRH in an episodic manner that intermittently stimulates the anterior pituitary to secrete gonadotropins in a pulsatile secretion pattern. The pulsatile secretion pattern of the gonadotropins LH and FSH changes over the menstrual cycle in normal women. Prolactin (Prl) is also secretes intermittently by the pituitary but the Prl pattern has minimal variation over the cycle. These signals from the brain (in the form of hormone secretion patterns) have effects on the ovary. FSH is necessary for recruitment and maturation of ovarian follicles. The midcycle LH and FSH surge initiate the genetic, biochemical, and endocrine events of ovulation. The corpus luteum is the principal source of progesterone (P) which is essential for nidation and maintenance of early pregnancy. Adequate corpus luteum function is dependent upon both pre-ovulatory follicular development and a balance between luteotrophic and luteolytic factors. The major luteotrophic factor appears to be LH. Prolactin appears to be capable of both stimulatory and inhibitory effects on corpus luteum function. The ovary, like the hypothalamic-pituitary unit, communicates with the latter via signals that are secretion patterns of reproductive hormones. Estradiol (E) and inhibin from the ovarian follicle and P from the corpus luteum modify the hormone signal from the brain either directly or through intermediate neurotransmitters, primarily endogenous opioid peptides and dopamine. These anatomic and hormonal factors comprise a physiologic unit. Our investigations to date and our proposed studies seek to increase our understanding of the functional physiology between the brain and the ovary in normal women and women with luteal phase deficiency (LPD). Our prior studies helped to elucidate the secretion patterns of LH, FSH, Prl and P and their end-organ effects. This research proposal focuses on several specific aspects of the hormone signal in normal women for further investigation: the intercycle FSH rise, the LH surge, and the luteotrophic effect of LH. Additional proposed studies in normal women are: the effects on LH, FSH, and Prl secretion and ovarian function of premature luteolysis and opioid antagonist treatment. In patients with LPD we will test their responsiveness to P negative feedback, opioid antagonist treatment, and dopamine antagonist treatment in terms of hormone secretion and ovarian response. Finally, we will examine the effects on gonadotropin secretion and ovarian function of drugs used in the treatment of LPD.
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