The objective of the proposed project is to define the molecular mechanisms by which the responsiveness of ovarian follicles and corpora lutea (CL) to gonado-hormones is regulated. The hormonal responsiveness of a tissue is as important in determining the magnitude of the response elicited as is the serum concentration of the hormone. Tissue responsiveness encompasses at least the hormone-receptor adenylyl cyclase and protein kinase enzyme systems. Emphasis is placed upon the regulation by luteinizing hormone, prolactin, estrogen, and the catecholamines of the presence, activity, and responsiveness of the receptor-coupled adenylyl cyclase and protein kinase enzyme systems in ovarian follicles and CL. The effect of various in vivo manipulations during different states of reproduction on the hormonal milieu surrounding ovarian tissues will be determined both by subsequent in vitro characterizations of the ovarian adenylyl cyclase and protein kinase enzyme systems and, when appropriate, by the steroidogenic response of these tissues. It is through such studies on the interregulation by all of the gonado-hormones of these key enzyme systems that we can understand the molecular mechanisms of action, and therefore the function, of the gonado-hormones in ovarian follicles and CL.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD011356-08
Application #
3311541
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1977-12-01
Project End
1986-02-28
Budget Start
1984-12-01
Budget End
1986-02-28
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
School of Medicine & Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Jackiw, V; Hunzicker-Dunn, M (1992) The regulatory subunit of the type II cAMP-dependent protein kinase in rabbit ovaries is the RII beta isoform. Biochem Biophys Res Commun 184:43-9
Jackiw, V; Hunzicker-Dunn, M (1992) Luteinization-associated changes in protein stability of the regulatory subunit of the type I cAMP-dependent protein kinase. J Biol Chem 267:14335-44
Maizels, E T; Miller, J B; Cutler Jr, R E et al. (1992) Estrogen modulates Ca(2+)-independent lipid-stimulated kinase in the rabbit corpus luteum of pseudopregnancy. Identification of luteal estrogen-modulated lipid-stimulated kinase as protein kinase C delta. J Biol Chem 267:17061-8
Hunzicker-Dunn, M; Chen, A; Jackiw, V et al. (1991) Luteal enzymes of the luteinizing hormone and beta-adrenergic signal transduction pathways in hypophysectomized rabbits do not require pituitary hormone support. Biol Reprod 44:609-19
Hunzicker-Dunn, M; Cutler Jr, R E; Maizels, E T et al. (1991) Isozymes of cAMP-dependent protein kinase present in the rat corpus luteum. J Biol Chem 266:7166-75
Ekstrom, R C; Hunzicker-Dunn, M (1990) Comparison of the luteinizing hormone-sensitive adenylyl cyclase of the pig ovarian follicle and corpus luteum and its susceptibility to in vitro hormone-dependent desensitization. Endocrinology 126:1191-8
Ekstrom, R C; Hunzicker-Dunn, M (1990) Opposing effects of ethanol on pig ovarian adenylyl cyclase desensitized by human choriogonadotropin or isoproterenol. Endocrinology 127:2578-86
Maizels, E T; Miller, J B; Cutler Jr, R E et al. (1990) Calcium-independent phospholipid/diolein-dependent phosphorylation of a soluble ovarian Mr 80,000 substrate protein: biochemical characteristics. Biochim Biophys Acta 1054:285-96
Hunzicker-Dunn, M; Lorenzini, N; Cutler, R E et al. (1989) Modulation of soluble ovarian adenosine 3',5'-monophosphate-dependent protein kinase activity during prepubertal development in the rat. II. Evaluation of the catalytic subunit inhibitor activity. Biol Reprod 40:486-94
Ekstrom, R C; Hunzicker-Dunn, M (1989) Guanosine triphosphate fulfills a complete and specific nucleotide requirement for luteinizing hormone-induced desensitization of pig ovarian adenylyl cyclase. Endocrinology 125:2470-4

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