Proenkephalin and opioid mu-receptor mRNA expression in ovine hypothalamusacross the estrous cycle

The neural mechanism underlying the preovulatory surge of gonadotropin-rele asing hormone (GnRH) and luteinizing hormone (LH) is thought to include red uced opioid inhibition of GnRH secretion (disinhibition). Possible mechanis ms for disinhibition include reduced endogenous opioid peptide or receptor mRNA expression. Proenkephalin and opioid mu -receptor mRNA expression were measured by in situ hybridization using S-35-labeled cRNA probes and compu ter-assisted grain counting in hypothalamic nuclei of ovary-intact ewes (n = 4) killed on day 10 of the luteal phase or 24 or 48 h into the follicular phase. In a second experiment, proenkephalin and mu -receptor mRNA express ion were compared in ewes killed on day 10 of the luteal phase or during th e preovulatory LH surge. Cells expressing proenkephalin mRNA were more wide ly distributed in ovine hypothalamus than previously described. in the peri ventricular nucleus, there was a significant reduction in the grain count p er cell and the number of labeled cells during the follicular phase and dur ing the LH surge, as compared to the luteal phase. In the ventromedial hypo thalamus, there was a significant reduction in the grain count per cell dur ing the follicular phase and LH surge as compared to the luteal phase, but no change in the number of labeled cells. No differences in proenkephalin m RNA expression were detected in the medial septum, diagonal band of Broca, preoptic area, anterior hypothalamic area or paraventricular nucleus across the estrous cycle. Cells expressing opioid mu -receptor mRNA were also wid ely distributed. No difference in mu -receptor mRNA expression was detected in the medial septum, diagonal band, medial preoptic area, anterior hypoth alamus or bed nucleus of the stria terminalis across the cycle. We conclude that in sheep, proenkephalin gene expression in the periventricular nucleu s and ventromedial hypothalamus is reduced during the follicular phase and at the time of the LH surge. This may be part of the neural mechanism under lying the GnRH/LH surge in this species. Copyright (C) 2001 S. Karger AG, B asel.