Effects of manipulating catecholamines on the incidence of the preovulatory surge of of luteinizing hormone and ovulation in the rat: evidence for a necessary involvement of hypothalamic adrenaline in the normal or 'midnight' surge.
The preovulatory surge of luteinizing hormone reaches a maximum at 18.00 h on the day of pro-oestrus in female rats maintained with regular lighting from 06.00 to 20.00 h. This surge is initiated by a discharge of luteinizing hormone-releasing hormone into hypophysial portal blood. In this study, drugs which affect catecholamine-mediated neurotransmission were administered on the day of pro-oestrus and the effects on serum concentrations of luteinizing hormone and on subsequent ovulation were observed. alpha-Methyl-p-tyrosine, diethyldithiocarbamate and SKF 64139 inhibit catecholamine synthesis at the level of tyrosine hydroxylase, dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase, respectively. Although alpha-methyl-p-tyrosine suppressed ovulation, it had a negligible effect on the incidence of the preovulatory surge. In contrast, the various treatments with diethyldithiocarbamate and SKF 64139 resulted in a minimal occurrence of the 18.00 h surge; at relatively low doses, however, these drugs frequently elicited a surge at 22.00 or 24.00 h which invariably resulted in ovulation. The failure of the surge after diethyldithiocarbamate or SKF 64139 was not associated with a loss of pituitary sensitivity to luteinizing hormone-releasing hormone. In terms of the hypothalamic concentration of dopamine, noradrenaline, adrenaline and 5-hydroxytryptamine at 18.00 h on pro-oestrus, the only common effect of diethyldithiocarbamate and SKF 64139, given in a dose which blocks the surge, was a severe depletion of adrenaline; alpha-methyl-p-tyrosine failed to produce this effect despite inducing a marked depression of dopamine and a moderate loss of noradrenaline. Neither the increase in hypothalamic dopamine after diethyldithiocarbamate, nor the alpha 2 receptor blocking properties of SKF 64139 appear to be relevant in this context since injections of L-dopa or piperoxane, an alpha 2 receptor antagonist, were without effect on the surge or ovulation. The failure of the surge after prazosin, an alpha 1 receptor antagonist, indicates that the function of adrenaline may be mediated postsynaptically by alpha 1 receptors. Clonidine, an alpha 2 receptor agonist which reduces the turnover rate of hypothalamic adrenaline, had effects of the surge and ovulation which were comparable to those of diethyldithiocarbamate and SKF 64139, the relatively low doses causing some of the surges to occur at 24.00 instead of 18.00 h and higher doses suppressing the surge at both times and thus preventing ovulation.(ABSTRACT TRUNCATED AT 400 WORDS)
D000588:Amines / Q000032:analysis; D000818:Animals; D002395:Catecholamines / Q000502:physiology*; D004031:Diestrus; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000502:physiology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology; D007031:Hypothalamus / Q000032:analysis / Q000502:physiology*; D007986:Luteinizing Hormone / Q000097:blood*; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D010060:Ovulation; D010903:Pituitary Gland, Anterior / Q000502:physiology; D011247:Pregnancy; D011359:Proestrus / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D000588:Amines; D002395:Catecholamines; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D007986:Luteinizing Hormone; D009638:Norepinephrine; D004837:Epinephrine