Opioid and neurotransmitter regulation of pituitary gonadotropin-releasing hormone (GnRH) receptors in the ovariectomized estradiol-treated rat: role of altered GnRH secretion

• Published in: Endocrinology (Philadelphia) Vol. 116; no. 3; p. 1003
• Main Authors: Barkan, A L, Duncan, J A, Schiff, M, Papavasiliou, S, Garcia-Rodriguez, A, Kelch, R P, Marshall, J C
• Format: Journal Article
• Language: English
• Published: United States 01.03.1985
• Subjects: Animals; Castration; Estradiol - pharmacology; Female; Hypothalamus, Middle - physiology; Morphine - pharmacology; Naloxone - pharmacology; Neurotransmitter Agents - physiology; Pituitary Gland - metabolism; Pituitary Hormone-Releasing Hormones - metabolism; Pituitary Hormone-Releasing Hormones - secretion; Rats; Receptors, Cell Surface - drug effects; Receptors, Cell Surface - metabolism
• DOI: 10.1210/endo-116-3-1003
• ISSN: 0013-7227

An acute transient fall in the number of pituitary GnRH receptors (GnRH-R) is observed before the preovulatory gonadotropin surge in cycling rats and before the afternoon daily gonadotropin surge in ovariectomized estradiol-treated rats. In the latter model, this fall can be reproduced by administration of the opioid antagonist naloxone, whereas the opioid agonist morphine acutely increases GnRH-R. In this study we investigated the mechanisms of this opioid effect and examined the effects of other neurotransmitter substances on modulation of pituitary GnRH-R. Administration of the dopaminergic agonists bromocriptine and L-dopa or the alpha-adrenergic receptor blocker phenoxybenzamine elevated GnRH-R acutely from average basal values of 240 +/- 22 and 254 +/- 21 fmol/mg protein to maximal values of 374 +/- 49, 441 +/- 67 and 461 +/- 75 fmol/mg, respectively, whereas the alpha-adrenergic agonist clonidine transiently decreased GnRH-R to 186 +/- 19 fmol/mg. Placement of radiofrequency lesions in the mediobasal hypothalamus or pretreatment with anti-GnRH serum completely abolished the ability of both morphine and naloxone to modulate the number of GnRH-R. These data indicate that the opioid-induced modulation of pituitary GnRH-R requires an intact hypothalamus and that both dopaminergic and alpha-adrenergic neurotransmitter systems may be involved. The final step of this action probably involves acute modulation of GnRH secretion (altered frequency and/or amplitude), which results in acute transient changes in the number of pituitary GnRH-R.