Are catechol oestrogens obligatory mediators of oestrogen action in the central nervous system? II. Potencies of natural and synthetic oestrogens for induction of gonadotrophin release and female sexual behaviour in the rat
MacLusky, N.J.; Krey, L.C.; Parsons, B.; Merriam, G.R.; Loriaux, D.L.; Pfeiffer, D.G.; Naftolin, F.
Journal of Endocrinology 110(3): 499-505
1986
ISSN/ISBN: 0022-0795 PMID: 3020145 DOI: 10.1677/joe.0.1100499Document Number: 433514
The effects of oestradiol-17 beta in facilitating gonadotropin release were compared with those of a group of oestrogens with a reduced affinity for oestrogen receptors (oestradiol-17 alpha ) or a reduced ability to act as substrates for catecholoestrogen formation (2-fluoro-oestradiol, 4-fluoro-oestradiol and moxoestrol (11 beta -methoxy-17 alpha -ethynyloestradiol)). Adult female rats were ovariectomised on the evening of dioestrus-I of the 4-day oestrous cycle and were implanted subcutaneously 12 h later with infusion pumps containing one of the test oestrogens or vehicle alone. Infusion rates for oestradiol-17 beta , moxoestrol, 2-fluoro-oestradiol and 4-fluoro-oestradiol were adjusted to given concentrations of nuclear oestrogen receptors in the brain and pituitary gland within the range of those found in intact female rats during pro-oestrus. Oestradiol-17 alpha was infused at the same and at a tenfold higher rate than that of oestradiol-17 beta ; neither of these treatments with oestradiol-17 alpha significantly increased brain or pituitary nuclear oestrogen receptor levels. On the day after the pump was implanted, samples of tail vein blood were withdrawn at 12.00, 14.00, 16.00 and 18.00 h for LH assay. All animals were then injected subcutaneously with 1 mg progesterone in propylene glycol, and were tested for sexual behaviour 5 h later. Oestradiol-17 beta , moxoestrol, 2-fluoro-oestradiol and 4-fluoro-oestradiol all elicited pronounced LH surges and facilitated progesterone-triggered proceptive and lordosis behaviour. By contrast, oestradiol-17 alpha was without effect on LH secretion and sexual behaviour. These results are consistent with the hypothesis that catecholoestrogen biosynthesis is not an obligatory step in the mechanism by which circulating oestrogens induce LH release and feminine sexual behaviour in the rat. .