Abstract

The objective of this application is to elucidate the mechanisms responsible for the differential secretion of FSH and LH. The first specific aim will test the hypothesis that the ability of specific GnRH pulse patterns to differentially stimulate FSHb and FSH secretion is mediated by changes in pituitary activin and follistatin (FS). The initial experiments will use a GnRH-deficient in vivo model to examine the effects of GnRH pulse patterns and gonadal steroids on mRNA levels of inhibin-bB, inhibin-a, and FSHb and FSH secretion. The next experiments will use in vivo and in vitro application of peptides and antisera to test the role of pituitary FS and activin in mediating the action of GnRH on FSH synthesis and secretion. The final studies in this specific aim will examine the hormonal role of inhibin by monitoring the pituitary effects of immunoneutralization of inhibin in females and test the hypothesis that testosterone blocks that action of inhibin by giving testosterone to females and anti-androgens to males. The second specific aim will make use of RT-PCR measurements of primary transcripts to assess the effect of GnRH pulse patterns and gonadal hormones on the transcription rate of the FSHb and LHb genes, using the same in vivo models as Specific Aim 1.

  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 #
5R01HD011489-23
Application #
6181347
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
De Paolo, Louis V
Project Start
1991-01-01
Project End
2003-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
23
Fiscal Year
2000
Total Cost
$246,675
Indirect Cost

  Institution

Name
University of Virginia
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904

  Publications

Burger, Laura L; Haisenleder, Daniel J; Aylor, Kevin W et al. (2008) Regulation of intracellular signaling cascades by GNRH pulse frequency in the rat pituitary: roles for CaMK II, ERK, and JNK activation. Biol Reprod 79:947-53
Haisenleder, D J; Burger, L L; Walsh, H E et al. (2008) Pulsatile gonadotropin-releasing hormone stimulation of gonadotropin subunit transcription in rat pituitaries: evidence for the involvement of Jun N-terminal kinase but not p38. Endocrinology 149:139-45
Burger, Laura L; Haisenleder, Daniel J; Wotton, Gordon M et al. (2007) The regulation of FSHbeta transcription by gonadal steroids: testosterone and estradiol modulation of the activin intracellular signaling pathway. Am J Physiol Endocrinol Metab 293:E277-85
Haisenleder, Daniel J; Aylor, Kevin W; Burger, Laura L et al. (2006) Stimulation of FSHbeta transcription by blockade of endogenous pituitary follistatin production: Efficacy of adenoviral-delivered antisense RNA in the rat. Endocrine 29:399-404
Haisenleder, D J; Burger, L L; Aylor, K W et al. (2005) Testosterone stimulates follicle-stimulating hormone beta transcription via activation of extracellular signal-regulated kinase: evidence in rat pituitary cells. Biol Reprod 72:523-9
Prendergast, Kathleen A; Burger, Laura L; Aylor, Kevin W et al. (2004) Pituitary follistatin gene expression in female rats: evidence that inhibin regulates transcription. Biol Reprod 70:364-70
Burger, Laura L; Haisenleder, Daniel J; Aylor, Kevin W et al. (2004) Regulation of luteinizing hormone-beta and follicle-stimulating hormone (FSH)-beta gene transcription by androgens: testosterone directly stimulates FSH-beta transcription independent from its role on follistatin gene expression. Endocrinology 145:71-8
Burger, L L; Haisenleder, D J; Dalkin, A C et al. (2004) Regulation of gonadotropin subunit gene transcription. J Mol Endocrinol 33:559-84
Haisenleder, D J; Burger, L L; Aylor, K W et al. (2003) Gonadotropin-releasing hormone stimulation of gonadotropin subunit transcription: evidence for the involvement of calcium/calmodulin-dependent kinase II (Ca/CAMK II) activation in rat pituitaries. Endocrinology 144:2768-74
Burger, Laura L; Dalkin, Alan C; Aylor, Kevin W et al. (2002) GnRH pulse frequency modulation of gonadotropin subunit gene transcription in normal gonadotropes-assessment by primary transcript assay provides evidence for roles of GnRH and follistatin. Endocrinology 143:3243-9

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