Modulation of synthesis and secretion of LHRH and LH through ovarian steroids: Altered secretion of LH affects ovarian follicular dynamics

The objectives of the experiments defined within this dissertation are to understand how ovarian steroids modulate synthesis and secretion of LH and LHRH. An additional objective is to determine how altered secretion of LH affects ovarian follicular dynamics. Our hypothesis is that ovarian steroids interact at different centers within the hypothalamic-pituitary-gonadal axis to modulate reproductive events. In the first experiment, a neuronal cell line (GT1-7) which secrets LHRH was utilized to establish effects of second messengers (Protein Kinase A and Protein Kinase C) on amounts of mRNA for protooncogenes and LHRH. Stimulation of GT1-7 cells with cAMP (PKA activator) enhanced mRNA for c-jun 9 h prior to a coordinate increase in mRNA for LHRH. Administration of TPA (PKC activator) to GT1-7 cells increased mRNA for c-fos at 3 h, while mRNA for LHRH was decreased by 48 h. We propose that second messengers affect mRNA for protooncogenes c-fos and c-jun which in turn regulate expression of mRNA for LHRH. The second experiment was designed to determine if rising concentrations of 17$\beta$-estradiol increased amounts of mRNA for gonadotropin subunits in cows. Amounts of mRNA for $\alpha,$ LH$\beta$ and FSH$\beta$ subunits were increased in ovariectomized cows compared to intact follicular phase controls and ovariectomized cows administered increasing concentrations of 17$\beta$-estradiol. We conclude that although secretion of LH and FSH are enhanced in ovariectomized cows administered 17$\beta$-estradiol, amounts of mRNA for all gonadotropin subunits are suppressed. The third experiment evaluated if concentrations of progesterone in circulation, through modulation of pulsatile secretion of LH, affected pattern of ovarian follicular growth. Cows were administered a low dose of progesterone (0.5PRID) or a greater dose of progesterone (2PRID) or had intact corpora lutea (controls). The low dose of progesterone resulted in enhanced frequency of LH pulses from the pituitary and large follicles with extended lifespans developed on the ovary. Cows in the 2PRID or CONT groups developed ovarian follicles that grew and became atretic, and thus had waves of ovarian follicular growth. Cows administered 0.5PRID had ovarian follicles with greater concentrations of LH receptors in thecal and granulosal cells and increased concentrations of 17$\beta$-estradiol, and androstenedione compared to other groups. We conclude that dose of progesterone in circulation, alters both pulsatile secretion of LH and biochemical composition of ovarian follicles