Ovarian function in humans, as well as a variety of other species, is primarily controlled by gonadotropins present in the blood stream. Since luteinizing hormone (LH) has been implicated as the major hormone involved in ovulation and steroid secretion, we have proposed experiments to examine factors regulating its synthesis and secretion.
The specific aims of this proposal address three potential mechanisms by which secretion of LH from the anterior pituitary gland may be regulated and include modulation of the: 1) number of receptors for GnRH; 2) rate of synthesis of LH; and 3) the number of cells synthesizing and secreting LH. To examine the effects of various stimuli known to influence the secretion of LH by the anterior pituitary gland, and without the confounding influence of the hypothalamus, we propose to utilize animals in which the hypothalamus has been surgically disconnected from the anterior pituitary gland for some of the experiments. Secondly, we propose to utilize cDNA probes to quantify messenger RNAs for the subunits of LH to determine the rate of transcription of the genes encoding for these RNAs. By quantifying the subunits of LH, we can examine the translation of mRNAs and indirectly estimate functionality of the subcellular compartments required for protein synthesis. Further, by quantifying the pituitary content of mature LH we can obtain an estimate of the rate at which the subunits are combined. Finally, we will attempt to produce monoclonal antibodies specific for gonadotrophs and to utilize these antibodies to determine if the number of gonadotrophs varies during different physiological states. We propose to combine an antibody specific for gonadotrophs with a toxin, thus producing an immunotoxin that will specifically kill gonadotrophs. We have chosen the ewe as a model for the proposed studies due to the extensive background information available, the ability to collect frequent blood samples for extended periods, the large quantity of adenohypophyseal tissue (equivalent to 1 g/animal), and the similarity of the mechanisms regulating reproductive function between ewes and women. We anticipate the proposed research will provide new, basic information that will be useful for developing more efficient and safer methods for regulating fertility in humans, meat- and milk-producing species and companion animals.
