Compromised reproductive function in adult female mice selectively expressing mutant ErbB-1 tyrosine kinase receptors in astroglia.
The ErbB-1 tyrosine kinase receptor plays critical roles in regulating physiological functions. This receptor-mediated signaling in astroglia has been implicated in controlling female sexual development via activating neurons that release LH-releasing hormone (LHRH), the neuropeptide required for the secretion of LH. It remains unknown whether astroglial ErbB-1 receptors are necessary for maintaining normal adult reproductive function. Here we provide genetic evidence that astroglia-specific and time-controlled disruption of ErbB-1 receptor signaling by expressing mutant ErbB-1 receptors leads to compromised reproduction due to alteration in LHRH neuron-controlled secretion of LH in adult female mice. Therefore, astroglial ErbB-1 receptors are required for controlling LHRH neuronal function and thus maintaining adult reproduction, suggesting that compromised astroglial ErbB-1 signaling may also contribute to reproductive abnormalities in aging females.
Li
Biao
B
Center for Human Molecular Genetics, Munroe-Meyer Institute and Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 68198-5455, USA.
Yang
Zhihui
Z
Hou
Jingwen
J
McCracken
April
A
Jennings
M Anita
MA
Ma
Mark Y J
MY
D000375:Aging / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004440:Ecdysone / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D030762:Estrous Cycle; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D017353:Gene Deletion; D015870:Gene Expression / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009928:Organ Specificity; D010053:Ovary / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012098:Reproduction / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013997:Time Factors
D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D004440:Ecdysone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D066246:ErbB Receptors