Actions of RU 38486 on progesterone facilitation and sequential inhibition of rat estrous behavior: correlation with neural progestin receptor levels.
The present study examined the actions of the antiprogestin RU 38486 on progesterone (P)-induced facilitation and sequential inhibition of estrous behavior and on brain cytosol progestin receptor (PR) levels in ovariectomized, estrogen-primed (0.5 micrograms of estradiol benzoate for 3 days) female rats. RU 38486 suppressed P-facilitated receptive and proceptive responses in a dose-dependent fashion when administered 1 hr prior to P. RU 38486 did not, however, block the sequential inhibitory effect of P. Indeed, when it was administered alone at a dose of 1 mg, animals were rendered behaviorally unresponsive to a P treatment 25 hr later. It is unclear whether RU 38486 is an agonist for P sequential inhibition of estrous behavior or if the apparent agonist action of RU 38486 actually results from a long-term antagonist effect. Estrogen-induced PRs remain elevated (35-55% above basal) in the hypothalamus (HYP) and preoptic area (POA) at 24 and 48 hr following the last estrogen injection. Thus P facilitation of estrous behavior is correlated with increased levels of cytosol PRs. RU 38486 reduced cytosol PRs in both brain regions to basal levels within 2 hr, and the levels remained suppressed 25 hr following the treatment. Hence there is a strong correlation between behavioral inhibition and suppressed cytosol PRs at both short (5 hr) and long (25 hr) intervals after RU 38486 administration. A P treatment which produced sequential inhibition of estrous responsiveness 24 hr later did not reduce the estrogen-induced level of cytosol PRs in either brain region. These results suggest that mechanisms in addition to induction of PRs may be necessary to ensure successful mating.
Vathy
I U
IU
Department of Psychiatry, Albert Einstein College of Medicine, Bronx, New York 10461.
Etgen
A M
AM
Barfield
R J
RJ
D000818:Animals; D001921:Brain / Q000187:drug effects*; D003600:Cytosol / Q000187:drug effects; D004963:Estrenes / Q000494:pharmacology*; D004971:Estrus / Q000187:drug effects*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects; D015735:Mifepristone; D011301:Preoptic Area / Q000187:drug effects; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011980:Receptors, Progesterone / Q000187:drug effects*; D012726:Sexual Behavior, Animal / Q000187:drug effects*
D004963:Estrenes; D011980:Receptors, Progesterone; D015735:Mifepristone; D011374:Progesterone