GENOMICS OF GnRH PRIMING

Project: Research project

Description

DESCRIPTION (provided by applicant): Gonadotropin releasing-hormone (GnRH) self priming and its cross talk with the progesterone receptor is a signal amplification mechanism that has demonstrated physiological relevance in rodent models as well as in humans. In priming, GnRH augments the luteinizing hormone (LH) release that occurs with subsequent pulses of GnRH, a phenomenon that contributes to the preovulatory LH surge. Priming appears to depend on early gene induction. It first occurs within 40 minutes of GnRH or progesterone exposure and requires transcription, but only for the first hour of induction. Furthermore, it has a unique physiological signature, being induced by either GnRH or progesterone and prevented by progesterone receptor antagonists even in the absence of progesterone. The overall hypothesis is that one consequence of a GnRH receptor-activated signaling pathway is progesterone-independent activation of the progesterone receptor resulting in GnRH self priming. The corollary to be tested in this proposal is that a subset of genes is activated by either GnRH or progesterone and this subset subserves the priming function in gonadotropes. In Aim I GnRH- or progesterone-induced global early gene programs in rat gonadotropes will be defined by microarray analysis; second stage studies will use quantitative real-time PCR to identify putative causative priming genes in this set that conform to the physiological signature of priming. Aim II will establish that the gene or genes identified in Aim I has/have an obligatory role in the priming function using a single cell model of exocytosis. All experiments will use rat anterior pituitary cell cultures enriched for gonadotropes. These studies represent new approaches to identify a long elusive but important target, which is a crucial component of the endocrine reproductive cycle. Additionally, in the process of identifying the genes responsible for priming, GnRH- and progesterone modulated early gene programs in primary gonadotropes will be defined; thus, an important database with broad application will be generated.
StatusFinished
Effective start/end date12/15/0311/30/06

Funding

  • National Institutes of Health: $117,148.00
  • National Institutes of Health: $129,273.00

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Genomics
Gonadotropin-Releasing Hormone
Progesterone
Genes
Progesterone Receptors
Luteinizing Hormone
LHRH Receptors
Exocytosis
Microarray Analysis
Real-Time Polymerase Chain Reaction
Rodentia
Cell Culture Techniques
Databases

ASJC

  • Medicine(all)