The long-term goal of this project is to elucidate the cellular mechanisms involved in modulation of the estradiol-induced preovulatory LH surge by progesterone or nonsteroidal antiestrogens. The observation that progesterone or synthetic progestins could block gonadotropin surges and ovulation provided the basis for the development of modern antifertility drugs, and the antiestrogens are also of clinical importance for treatment of infertility. Conditions have been established in this laboratory for demonstration of inhibition of estradiol-induced LH surges by progesterone or antiestrogens (nafoxidine or 4-hydroxytamoxifen) or for facilitation of these surges by progesterone in the immature (28-30 day-old) female rat. These paradigms will be employed to examine the possible effects of progesterone or hydroxytamoxifen on the following parameters: (1) steady-state levels of messenger RNA for the rat alpha and LH beta subunits using specific cDNA probes corresponding to portions of these genes and RNA blot hybridization; (2) changes in transcription of the genes encoding the rat alpha and LH beta subunits using nuclear runoff (in vitro) transcription assays; (3) pituitary responsiveness to a """"""""physiologic"""""""" challenge with exogenous gonadotropin-releasing hormone (GnRH); (4) concentration of progestin receptors in cell cytosols and nuclei from the hypothalamus, preoptic area, and pituitary of rats treated with various classes of steroids to either inhibit or facilitate LH surges (to compare basal and estrogen-inducible progestin receptors in these tissues). Progestin receptors will be quantitated by in vitro exchange with tritiated high affinity synthetic progestins (R5020 or ORG 2058). Where appropriate intrapituitary LH content and serum concentrations of LH and GnRH will be measured by radioimmunoassay.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD012099-10
Application #
3311782
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1978-09-29
Project End
1990-01-31
Budget Start
1989-02-01
Budget End
1990-01-31
Support Year
10
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Montefiore Medical Center (Bronx, NY)
Department
Type
DUNS #
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Plant, T M; Winters, S J; Attardi, B J et al. (1993) The follicle stimulating hormone-inhibin feedback loop in male primates. Hum Reprod 8 Suppl 2:41-4
Attardi, B; Marshall, G R; Zorub, D S et al. (1992) Effects of orchidectomy on gonadotropin and inhibin subunit messenger ribonucleic acids in the pituitary of the rhesus monkey (Macaca mulatta). Endocrinology 130:1238-44
Winters, S J; Ishizaka, K; Kitahara, S et al. (1992) Effects of testosterone on gonadotropin subunit messenger ribonucleic acids in the presence or absence of gonadotropin-releasing hormone. Endocrinology 130:726-34
Attardi, B; Vaughan, J; Vale, W (1992) Regulation of FSH beta messenger ribonucleic acid levels in the rat by endogenous inhibin. Endocrinology 130:557-9
Ishizaka, K; Kitahara, S; Oshima, H et al. (1992) Effect of gonadotropin-releasing hormone pulse frequency on gonadotropin secretion and subunit messenger ribonucleic acids in perifused pituitary cells. Endocrinology 130:1467-74
Attardi, B; Keeping, H S; Winters, S J et al. (1991) Comparison of the effects of cycloheximide and inhibin on the gonadotropin subunit messenger ribonucleic acids. Endocrinology 128:119-25
Keeping, H S; Winters, S J; Attardi, B et al. (1990) Developmental changes in testicular inhibin and androgen-binding protein during sexual maturation in the cynomolgus monkey, Macaca fascicularis. Endocrinology 126:2858-67
Attardi, B; Miklos, J (1990) Rapid stimulatory effect of activin-A on messenger RNA encoding the follicle-stimulating hormone beta-subunit in rat pituitary cell cultures. Mol Endocrinol 4:721-6
Attardi, B; Fitzgerald, T (1990) Effects of progesterone on the estradiol-induced follicle-stimulating hormone (FSH) surge and FSH beta messenger ribonucleic acid in the rat. Endocrinology 126:2281-7
Hoffman, G E; Lee, W S; Attardi, B et al. (1990) Luteinizing hormone-releasing hormone neurons express c-fos antigen after steroid activation. Endocrinology 126:1736-41

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