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Androgen Receptor's Role in GnRH Receptor Gene Regulation and Mouse Fertility

  • Author(s): Shojaei, Shadi
  • et al.
Abstract

Gonad-derived sex steroids have been known to play an active role in the regulatory hormone feedback loop within the hypothalamic-pituitary-gonad (HPG) Axis. At the pituitary level, sex steroids regulate gonadotropin expression through regulation of the gonadotropin- releasing hormone (GnRH) receptor. Androgens in particular have been shown to suppress Luteinizing Hormone (LH) release while increasing Follicle-Stimulating Hormone (FSH) release. However, the mechanism of gonadotropin regulation by androgens remains largely unknown. Androgens are known to affect change in target cells through binding androgen receptor (AR), which has been shown to induce expression of GnRHR in pituitary gonadotropes in vivo. AR is expressed in various tissues and affects many reproductive functions. While the physiological role of AR has been partially studied through generation of whole- body and gonad-specific AR knockout (ARKO) mice, the role of pituitary-specific AR has not been addressed. My project therefore has centered on extrapolating a more detailed mechanism of AR action in regulating androgen- induced GnRHR expression, as well as its pituitary- specific role in mouse reproductive physiology. To that end, the immortalized gonadotrope L[Beta]T2 cell line has proven an effective context for our transcriptional studies. The generation of a novel pituitary-specific AR knockout mouse line labeled ARF/[alpha]GSUiCRE also served as an instrumental model for the analysis of the physiological impact of pituitary derived AR

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