Altered gene activity of epidermal growth factor receptor (ErbB-1) in the hypothalamus of aging female rat is linked to abnormal estrous cycles.
Activation of the ErbB-1 receptor is necessary for initiating mammalian female puberty by stimulating the release of LH-releasing hormone. It remains unclear whether ErbB-1 is also required in governing reproduction during adulthood and whether altered ErbB-1 signaling is linked to changes in gonadotropin secretion in aging females. The present study examined these issues. RT-PCR was employed to determine changes in ErbB-1 mRNA levels during proestrus in both young adult (YA) and middle-aged (MA) female rats. Before the LH surge, expression levels in the preoptic area of YA rats increased to a maximal value. No such increase in ErbB-1 mRNA was found in MA rats. This difference was confirmed by the analysis of in situ hybridization histochemistry, where a stronger mRNA signal was observed in the preoptic area of YA rats compared with MA females. ErbB-1 protein levels measured by Western blot reflected this difference. A peak level of ErbB-1 mRNA in the median eminence-arcuate nucleus was detected at 0800 h in YA rats, but it was delayed in MA animals. There were intense ErbB-1 mRNA-positive cells in the arcuate nucleus. Pharmacological blockade of ErbB-1 receptor-mediated signal transduction resulted in the disruption of estrous cyclicity in YA rats. These results indicate that ErbB-1 receptors are necessary for maintaining normal estrous cycles. Consequently, age-related alterations in hypothalamic ErbB-1 gene activity may contribute to a delayed preovulatory LH secretion in aging females. Thus, the ErbB-1 signaling system plays an important role in the control of female reproduction during adulthood.
Hou
Jingwen
J
Center for Human Molecular Genetics and Department of Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 68198-5455, USA.
Li
Biao
B
Yang
Zhihui
Z
Fager
Nicole
N
Ma
Mark Y J
MY
D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D030762:Estrous Cycle / Q000235:genetics / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D012739:Gonadal Steroid Hormones / Q000097:blood; D007031:Hypothalamus / Q000254:growth & development* / Q000378:metabolism*; D017403:In Situ Hybridization; D011359:Proestrus / Q000235:genetics / Q000502:physiology; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D012739:Gonadal Steroid Hormones; D015347:RNA Probes; D012333:RNA, Messenger; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases