Gonadotropin-induced Steroidogenesis and Downstream Signals Leading to Oocyte Maturation

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Title: Gonadotropin-induced Steroidogenesis and Downstream Signals Leading to Oocyte Maturation
Author: Evaul, Kristen Elizabeth
Abstract: The Hammes laboratory is interested in understanding the process of steroid -mediated oocyte maturation . This includes examining both steroid production and steroid signaling . In these studies , gonadotropin -induced steroid production was examined in the gonads using mouse models , as well as steroid -induced oocyte maturation in frog models . cAMP signaling is known to be important for steroid production , but further downstream pathways were not well characterized . These studies illuminate other downstream signaling pathways triggered by luteinizing hormone (LH ) that regulate steroid production in the testes using Leydig cells , which are the primary steroidogenic cells in the testes . A novel downstream pathway was found involving epidermal growth factor receptor (EGFR ) transactivation , downstream mitogen -activated protein kinase (MAPK ) and steroidogenic acute regulatory protein (StAR ) activation that was essential for short , but not long -term LH -induced steroidogenesis in MLTC -1 and primary mouse leydig cells . Despite this discrepancy in vitro , EGFR signaling was required in vivo for testicular testosterone production . To study the effects of steroids on oocyte maturation , the Xenopus laevis frog model was used . It has been shown that G -beta gamma , as well as other signals , keep the oocyte in meiotic arrest . Steroids block this constitutive signal , leading to oocyte maturation . To directly measure rapid changes in G -beta gamma signaling in oocytes , G -beta gamma sensitive -inward rectifying potassium channel currents (GIRKS ) were exogenously expressed in Xenopus oocytes . Adding testosterone , the physiologic mediator of oocyte maturation in Xenopus , decreased the G -beta gamma mediated signal . This happened rapidly supporting the well known idea that maturation is a transcription -independent process . It was also seen that the classical androgen receptor (AR ) was being used for this process . When the AR was knocked down , testosterone could only decrease GIRK signal at higher concentrations . This showed that testosterone is working , at least partially , through the AR . These studies may help elucidate novel targets for polycystic ovary syndrome (PCOS ) , which is characterized by excess androgen due to improper steroid production .
URI: http : / /hdl .handle .net /2152 .5 /639
Date: 2009-01-09


Gonadotropin-induced Steroidogenesis and Downstream Signals Leading to Oocyte Maturation. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /639 .

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