Date of Award

9-1-2020

Degree Name

Doctor of Philosophy

Department

Molecular, Cellular, and Systemic Physiology

First Advisor

Narayan, Prema

Abstract

Constitutively activating mutations in luteinizing hormone receptor (LHCGR) cause a condition called familial male-limited precocious puberty (FMPP) characterized by elevated levels of testosterone, Leydig cell hyperplasia and precocious puberty. Our lab has generated a mouse model for FMPP – KiLHRD582G which exhibit similar phenotypes seen in humans. Earlier studies in our lab showed KiLHRD582G mice exhibit progressive infertility in spite of normal sperm production, motility and accessory gland function. Sexual behavior studies suggested erectile dysfunction and morphological changes in penile bodies were observed. As KiLHRD582G mice have elevated levels of testosterone, this study investigated the effect of high testosterone levels on causing morphological changes in penile body resulting in impairment of erectile function. Data from this study shows that androgens are responsible for inducing morphological changes in the penile body and these changes along with a dysregulated nitric oxide (NO) signaling pathway for smooth muscle relaxation in KiLHRD582G mice result in erectile dysfunction. These findings demonstrate the effect of constitutively activating LHCGR mutations/high testosterone levels in male sexual dysfunction and are clinically important in the context of understanding potential infertility in FMPP patients at middle or older ages.

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