Ovarian regulation of neuromedin U and its local actions in the ovary, mediated through neuromedin U receptor 2
| Autor: | Ting-Yu Lin, Fang Ju Wu, Wei Yu Lee, Chih Lun Hsiao, Ching Wei Luo |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
endocrine system
medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism media_common.quotation_subject Primary Cell Culture Gene Expression Neuropeptide Superovulation Ovary Biology Chorionic Gonadotropin Energy homeostasis Rats Sprague-Dawley Neuromedin U receptor Physiology (medical) Internal medicine Cyclic AMP medicine Animals media_common Granulosa Cells Neuropeptides Appetite Rats Receptors Neurotransmitter Endocrinology medicine.anatomical_structure Theca Cells Anorexigenic peptide Reproductive Control Agents Female Signal transduction Neuromedin U Signal Transduction |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 304:E800-E809 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.00548.2012 |
| Popis: | Neuromedin U (NMU) was originally identified as an anorexigenic peptide that modulates appetite as well as energy homeostasis through the brain-gut axis. Although growing evidence has linked NMU activity with the development of female reproductive organs, no direct expression of and function for NMU in these organs has been pinpointed. Using a superovulated rat model, we found that NMU is directly expressed in the ovary, where its transcript level is tightly regulated by gonadotropins. Ovarian microdissection and immunohistochemical staining showed clearly that NMU is expressed mainly in theca/interstitial cells and to a moderate extent in granulosa cells. Primary cell studies together with reporter assays indicated the Nmu mRNA level in these cells is strongly induced via cAMP signaling, whereas this increase in expression can be reversed by the degradation message residing within its 3′-untranslated region, which recruits cis-acting mRNA degradation mechanisms, such as the gonadotropin-induced zinc finger RNA-binding protein Zfp36l1. This study also demonstrated that NMUR2, but not NMUR1, is the dominant NMU receptor in the ovary, where its expression is restricted to theca/interstitial cells. Treatment with NMU led to induction of the early response c- Fos gene, phosphorylation of extracellular signal-regulated kinase 1/2, and promotion of progesterone production in both developing and mature theca/interstitial cells. Taken as a whole, this study demonstrates that NMU and NMU receptor 2 compose a novel autocrine system in theca/interstitial cells in which the intensity of signaling is tightly controlled by gonadotropins. |
| Databáze: | OpenAIRE |
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