Progesterone substitutes: cGMP mediation

Over the past 20 years many investigators have shown that one can facilitate sexual receptivity in estrogen-primed rats either by giving progesterone or a drug which stimulates or inhibits a neurotransmitter system. Drugs which have been reported to substitute for progesterone include cholinergic agonists, serotonergic agonists and antagonists, dopaminergic agonists and antagonists, opiate antagonists, neurohormones, pituitary, ovarian and adrenal hormones and drugs that interact with cyclic nucleotide systems. Most of the drugs that are active are known to increase neural levels of cyclic GMP either by acting on guanylate cyclase or on phosphodiesterase. We propose that the cGMP system mediates the common behavioral effect of the wide variety of drugs that facilitate receptivity.