Abstract

The objectives of this project are to investigate the factors that differentially regulate the storage, synthesis, and secretion of the gonadotropins, LH and FSH. Five interrelated specific aims are proposed. The first is to discover the site of delay in LH rise in female rats in response to removal of gonadal negative feedback. In vitro tests of hypothalami in a perifusion culture system will be used to determine whether there is a sex difference in GnRH secretion post-gonadectomy.
The second aim i s to examine pituitary, gonadal, and adrenal factors which regulate inhibin synthesis and secretion.
The third aim i s to discover the role of progesterone feedback on differential LH/FSH secretion using the progesterone receptor antagonist RU486.
The fourth aim i s to study the site of glucocorticoid differential regulation of LH and FSH synthesis and secretion. An ectopic pituitary transplant model will be used to examine whether the pituitary is the site of suppression by glucocorticoids of the response of LH to GnRH. The fifth aim is to investigate the site of action of hyperprolactinemia in the preferential suppression of LH over FSH secretion.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD007504-19
Application #
3310709
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1977-06-01
Project End
1996-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
19
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Northwestern University at Chicago
Department
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60201

  Publications

Szabo, M; Kilen, S M; Nho, S J et al. (2000) Progesterone receptor A and B messenger ribonucleic acid levels in the anterior pituitary of rats are regulated by estrogen. Biol Reprod 62:95-102
Szabo, M; Kilen, S M; Saberi, S et al. (1998) Antiprogestins suppress basal and activin-stimulated follicle-stimulating hormone secretion in an estrogen-dependent manner. Endocrinology 139:2223-8
Schwartz, N B; Szabo, M; Verina, T et al. (1998) Hypothalamic-pituitary-gonadal axis in the mutant weaver mouse. Neuroendocrinology 68:374-85
Ringstrom, S J; Szabo, M; Kilen, S M et al. (1997) The antiprogestins RU486 and ZK98299 affect follicle-stimulating hormone secretion differentially on estrus, but not on proestrus. Endocrinology 138:2286-90
Woodruff, T K; Besecke, L M; Groome, N et al. (1996) Inhibin A and inhibin B are inversely correlated to follicle-stimulating hormone, yet are discordant during the follicular phase of the rat estrous cycle, and inhibin A is expressed in a sexually dimorphic manner. Endocrinology 137:5463-7
Knox, K L; Ringstrom, S J; Szabo, M et al. (1996) RU486 on an estrogen background blocks the rise in serum follicle-stimulating hormone induced by antiserum to inhibin or ovariectomy. Endocrinology 137:1226-32
Szabo, M; Knox, K L; Ringstrom, S J et al. (1996) Mechanism of the inhibitory action of RU486 on the secondary follicle-stimulating hormone surge. Endocrinology 137:85-9
McAndrews, J M; Ringstrom, S J; Dahl, K D et al. (1994) Corticosterone in vivo increases pituitary follicle-stimulating hormone (FSH)-beta messenger ribonucleic acid content and serum FSH bioactivity selectively in female rats. Endocrinology 134:158-63
Luderer, U; Schwartz, N B (1994) Acute changes in pulsatile LH and FSH secretion after ovariectomy in rats: treatment with oestradiol for 24 h suppresses LH, but not FSH, for at least 48 h. J Reprod Fertil 100:613-21
Knox, K L; Ringstrom, S J; Schwartz, N B (1993) RU486 blocks the effects of inhibin antiserum or luteinizing hormone on the secondary follicle-stimulating hormone surge. Endocrinology 133:277-83

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