Induction of LH hypersecretion in cyclic rats during the afternoon of oestrus by oestrogen in conjunction with progesterone antagonism or opioidergic blockade

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Abstract
The pro-oestrous secretion of progesterone that follows the LH surge in the rat limits the expression of the daily signal for LH surge initiation until the following oestrous cycle. This study explored the role of endogenous opioid peptides in the extinction by progesterone of the signal for the LH surge induced by oestrogen. Intact cyclic rats underwent external jugular venous cannulation on dioestrus, and were allowed to elicit a spontaneous pro-oestrous LH surge. On the afternoon of pro-oestrus, rats received an s.c. injection of oestradiol and an s.c. injection of either oil, 17β-hydroxy-11β-(4-dimethylaminophenyl)17α-(prop-1-ynyl)oestra-4,9,dien-3-one (RU 486; a synthetic anti-progestin), or N-cyclopropylmethyl-6-desoxy-6-methylene-noroxy-morphone (nalmefene; a long-acting opiate antagonist). Repeat doses of each were administered on the morning of oestrus to maintain increased oestrogen levels, and either progesterone or opioidergic blockade. Plasma was obtained from 13.00 to 19.00 h on oestrus for determination of the concentration of rat LH. Rats treated with oestradiol alone demonstrated consistently low concentrations of LH throughout the afternoon of oestrus. Rats treated with both oestradiol and either RU 486 or nalmefene demonstrated spontaneous augmentations of rat LH concentration during the afternoon of oestrus, which, although of diminished amplitude as compared with that seen in pro-oestrus, were consistent with a reactivation of the LH surge-generating mechanism. Rats treated with nalmefene in the absence of oestradiol were unable to augment LH secretion spontaneously. These experiments suggest that antagonism of progesterone action at the time of the LH surge prevents the extinction of the LH surge signal, so that it may be reactivated the next day by exogenous oestrogen. They similarly demonstrate that persistent opioidergic antagonism will permit oestrogen to reactivate the daily LH surge signal. The similar properties of an anti-progestin and an anti-opiate in this study suggest that the pro-oestrous progesterone rise extinguishes consecutive daily LH surges, in part, through increases in opioidergic tone. J. Endocr. (1988) 117, 229–235