Abstract

Using female sheep as the experimental model, this amended proposal will test the hypothesis that normally occurring changes in FSH heterogeneity are of functional significance , with increases in biopotency associated with the onset of puberty and the preovulatory period. The goals are to: (1) establish the modulatory role of estradiol in mediating FSH heterogeneity, (2) determine nature of FSH isoforms secreted during different phases of puberty and ovulatory cyclicity. (3) reveal the role of FSH heterogeneity in the initiation of the pubertal process through administration of different isoform mixes of recombinant-produced FSH to immature GnRH antagonist-treated lambs and (4) establish if freshly secreted non-metabolized, FSH isoforms in hypothalamo-pituitary portal plasma can effect different biological responses at the target site.

  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 #
5R01HD023812-06
Application #
2655119
Study Section
Reproductive Biology Study Section (REB)
Project Start
1988-09-01
Project End
2001-01-31
Budget Start
1998-02-01
Budget End
2001-01-31
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Pediatrics
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Padmanabhan, V; Karsch, F J; Lee, J S (2002) Hypothalamic, pituitary and gonadal regulation of FSH. Reprod Suppl 59:67-82
Padmanabhan, V; Christman, G M; Randolph, J F et al. (2001) Dynamics of bioactive follicle-stimulating hormone secretion in women with polycystic ovary syndrome: effects of estradiol and progesterone. Fertil Steril 75:881-8
Jansen, H T; West, C; Lehman, M N et al. (2001) Ovarian estrogen receptor-beta (ERbeta) regulation: I. Changes in ERbeta messenger RNA expression prior to ovulation in the ewe. Biol Reprod 65:866-72
West, C; Foster, D L; Evans, N P et al. (2001) Intra-follicular activin availability is altered in prenatally-androgenized lambs. Mol Cell Endocrinol 185:51-9
Timossi, C M; Barrios-de-Tomasi, J; Gonzalez-Suarez, R et al. (2000) Differential effects of the charge variants of human follicle-stimulating hormone. J Endocrinol 165:193-205
Padmanabhan, V; Lee, J S; Beitins, I Z (1999) Follicle-stimulating isohormones: regulation and biological significance. J Reprod Fertil Suppl 54:87-99
Crowe, M A; Padmanabhan, V; Mihm, M et al. (1998) Resumption of follicular waves in beef cows is not associated with periparturient changes in follicle-stimulating hormone heterogeneity despite major changes in steroid and luteinizing hormone concentrations. Biol Reprod 58:1445-50
Crowe, M A; Padmanabhan, V; Hynes, N et al. (1997) Validation of a sensitive radioimmunoassay to measure serum follicle-stimulating hormone in cattle: correlation with biological activity. Anim Reprod Sci 48:123-36
Ulloa-Aguirre, A; Midgley Jr, A R; Beitins, I Z et al. (1995) Follicle-stimulating isohormones: characterization and physiological relevance. Endocr Rev 16:765-87
Hassing, J M; Kletter, G B; I'Anson, H et al. (1993) Pulsatile administration of gonadotropin-releasing hormone does not alter the follicle-stimulating hormone (FSH) isoform distribution pattern of pituitary or circulating FSH in nutritionally growth-restricted ovariectomized lambs. Endocrinology 132:1527-36

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