As many as 15 percent of couples are evaluated at some time for a fertility disturbance. Of these, 40 percent are male factor infertility, and in another 20 percent the infertility is unexplained. Evidence that sperm counts have declined substantially in the twentieth century adds further significance to research in male reproductive health. The long term goal of this project is to understand the endocrine aspects of human male infertility by analyzing the mechanisms involved in the testicular control of gonadotropin secretion. Most of what is known about the cellular and molecuar biology of gonadotropin secretion is from experiments using rats and rat pituitary cells. But our research indicates that the control mechanisms regulating gonadotropin secretion in male rats may not always be applicable to men. Herein we propose the use of pituitary cell cultures from the nonhuman male primate as a model of the human hypothalamic-pituitary unit in an effort to understand gonadotropin secretion in normal and infertile men. Experiments will be conducted using monolayer cultures as well as perifused pituitary cells stimulated with pulses of GnRH. The major endpoints to be examined include gonadotropin secretion and subunit gene expression, GnRH receptors and follistatin mRNA.
The aims of the current proposal are: 1) To examine the effects of recombinant inhibin-B and recombinant inhibin-A in the presence or absence of activin-A on gonadotropin secretion and subunit gene expression in primate pituitary cells, 2) To determine whether GnRH pulse frequency differentially regulates the secretion of FSH and LH in perifused primate pituitary cells, and to probe the role of activin, inhibin and follistatin in this regulation, and 3) To determine why estradiol but not androgens inhibit gonadotropin secretion in primate pitutiary cells. The information to be derived from these studies should provide insight into the endocrine abnormalities in human male infertilty which cannot be learned from studies in cell lines or rats, or through human investigation.
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