The long-range goal of this proposal remains an understanding of prolactin action on the ovaries of higher mammals. We have shown that granulosa cells from porcine ovaries contain prolactin receptors and that these receptors are under control of hormonal and developmental influences in vivo and in vitro. In addition to prolactin receptors, there are important intracellular control points which regulate the action of prolactin on these cells. Despite comparable receptor levels, immature granulosa cells are inhibited whereas luteinizing granulosa cells are stimulated by prolactin. Estrogens seem critical to prolactin action in both cell-types, reversing the inhibitory effect and enhancing the stimulatory effect of prolactin. We will continue to probe the biochemistry of these prolactin actions, emphasizing the prolactin-estradiol interaction through studies of prolactin modulation of estrogen receptors and estrogen-mediated biochemical effects. Specifically, we will delineate the effects of prolactin, estrogen, and their interaction on cholesterol transport, metabolism, and utilization for steroidogenesis as well as the cyclic AMP/protein kinase system and the steroidogenic enzymes. Later in the grant period, we will study these questions in more refined preparations of follicular cells and ascertain the influence of follicular atresia on these hormonal effects. These data will be supplemented by studies in intact porcine follicles in which the interrelationship of steroid secretion and action can be studied more physiologically. In this latter phase of the work, we will study androgen and estrogen secretion and make estimates of steroidogenic enzymes and polypeptide receptors by cytochemistry and autoradiography, respectively, in addition to the endpoints above. This project may develop new insights into the pathophysiology of the galactorrhea-amenorrhea syndrome, a common cause of anovulation and infertility in humans.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD010122-09
Application #
3311225
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1979-09-30
Project End
1988-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
9
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Spicer, L J; Hammond, J M (1989) Regulation of ovarian function by catecholestrogens: current concepts. J Steroid Biochem 33:489-501
Spicer, L J; Hammond, J M (1989) Catecholestrogens inhibit proliferation and DNA synthesis of porcine granulosa cells in vitro: comparison with estradiol, 5 alpha-dihydrotestosterone, gonadotropins and catecholamines. Mol Cell Endocrinol 64:119-26
Spicer, L J; Hammond, J M (1989) Mechanism of action of 2-hydroxyestradiol on steroidogenesis in ovarian granulosa cells: interactions with catecholamines and gonadotropins involve cyclic adenosine monophosphate. Biol Reprod 40:87-95
Spicer, L J; Hammond, J M (1988) Effects of 2-hydroxyestradiol on the number of granulosa cell beta-adrenergic receptors. Endocrinology 122:2710-7
Spicer, L J; Hammond, J M (1988) Comparative effects of androgens and catecholestrogens on progesterone production by porcine granulosa cells. Mol Cell Endocrinol 56:211-7
Spicer, L J; Hammond, J M (1987) Catecholestrogens stimulate progestin secretion by cultured porcine granulosa cells. Mol Cell Endocrinol 50:139-47
Spicer, L J; Walega, M A; Hammond, J M (1987) Metabolism of [3H]2-hydroxyestradiol by cultured porcine granulosa cells: evidence for the presence of a catechol-O-methyltransferase pathway and a direct stimulatory effect of 2-methoxyestradiol on progesterone production. Biol Reprod 36:562-71
Hsu, C J; Hammond, J M (1987) Concomitant effects of growth hormone on secretion of insulin-like growth factor I and progesterone by cultured porcine granulosa cells. Endocrinology 121:1343-8
Spicer, L J; Hammond, J M (1987) 2-Hydroxyestradiol modulates a facilitative action of catecholamines on porcine granulosa cells. Endocrinology 120:2375-82
Mondschein, J S; Hammond, J M; Weisz, J (1987) Characteristics of estrogen-2/4-hydroxylase of porcine ovarian follicles: influence of steroidal and non-steroidal agents on the activity of the enzyme in vitro. J Steroid Biochem 26:121-4

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