Steroid control of gonadotropin-releasing hormone secretion: associated changes in pro-opiomelanocortin and preproenkephalin messenger RNA expression in the ovine hypothalamus.
The endogenous opioid peptides have been implicated in mediating the actions of estrogen and progesterone on GnRH release. We used in situ hybridization histochemistry to determine whether steroid-induced changes in GnRH/LH release in the female sheep are associated with changes in the cellular mRNA content of the precursors for beta-endorphin (pro-opiomelanocortin; POMC) and met-enkephalin (pre-proenkephalin; PENK). Two specific hypotheses were tested. First, that the inhibitory actions of progesterone are associated with an increase in opioid gene expression in specific hypothalamic nuclei. Our data support this hypothesis. Thus, an increase in progesterone was associated with increased POMC gene expression in the arcuate nucleus and PENK in the paraventricular nucleus. Further, the increase in POMC was restricted to regions of the arcuate nucleus that contain steroid sensitive beta-endorphin neurons. Our second hypothesis, that gene expression for the two opioid precursors would decrease prior to the start of the estradiol-stimulated GnRH surge, was not supported. Rather, POMC (but not PENK) gene expression in the arcuate nucleus was significantly higher in estradiol-treated animals than controls at the peak of the GnRH surge. These data suggest that beta-endorphin neurons in subdivisions of the arcuate nucleus and enkephalin neurons in the paraventricular nucleus are part of the neural network by which progesterone inhibits LH release. While enkephalin neurons may not play a role in estrogen positive feedback, increases in POMC mRNA in the arcuate nucleus at the time of the GnRH peak may be important for replenishing beta-endorphin stores and terminating estrous behavior.
Taylor
James A
JA
Laboratory of Neuroendocrinology, and Cognitive and Developmental Neuroscience, The Babraham Institute, Babraham, Cambridge CB2 4AT, United Kingdom.
Goubillon
Marie-Laure
ML
Broad
Kevin D
KD
Robinson
Jane E
JE
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D004745:Enkephalins / Q000235:genetics* / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D008183:Luteal Phase; D010052:Ovariectomy; D011333:Pro-Opiomelanocortin / Q000235:genetics* / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger; D034561:Sheep, Domestic; D013256:Steroids / Q000378:metabolism*
D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D013256:Steroids; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D011333:Pro-Opiomelanocortin; C033660:preproenkephalin