Ovine gonadotrophs in pituitary cell culture are affected by estrogens in two ways which are easily measured. Estrogens can (1) decrease spontaneous FSH secretion (greater than 90% between 2 and 30 h) and (2) increase gonadotroph sensitivity to GNRH within 6 h (approx. 20-fold at 10 to the minus 10th power M LHRH). Our research is designed to use ovine gonadotrophs in cell culture for studying estrogen action in gonadotrophs and the control of gonadotrophin secretion in general, with an emphasis on FSH. Immediate aims are to characterize the following aspects of FSH biosynthesis (1) mRNA production (using hybridization probes from cloned cDNAs or genes coding for FSH subunits) and (2) translation of the subunit mRNAs with subsequent processing and secretion. The effects of estrogen on each step will be determined. Efforts will also be made to evaluate other physiologically important substances, such as inhibin and LHRH, or FSH biosynthesis and secretion. Finally, efforts will be made to evaluate LHRH binding or internalization as a possible site of estrogen action in terms of gonadotroph sensitization to LHRH. These studies may also lead to basic knowledge about LHRH binding which may, in turn, be used to develop effective methods for enriching gonadotrophs by using LHRH-specific methods. Detailed knowledge of estrogen action in ovine gonadotrophs may add to the general understanding of eucaryotic gene regulation and may, at a clinical level, provide information useful for treating those mammary cancers which are estrogen sensitive (60 to 70%). Furthermore, a clear understanding of the actions of estrogen, inhibin, and other substances on gonadotrophin secretions may yield data relevant to (1) correction of human reproductive disfunction, (2) reliable and safer birth control methods, and (3) increasing reproductive capacity of animals raised for food.
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