Role of serotonin in estrogen-progesterone induced luteinizing hormone release in ovariectomized rats

Pharmacological agents were used to manipulate the surge of luteinizing hormone (LH) induced by progesterone in ovariectomized rats primed with estradiol benzoate. The LH surge was abolished with p-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase, and restored by 5-hydroxytryptophan, a serotonin precursor. Serotonin receptor agonists, quipazine and N-N-dimethyl-5-methoxytryptamine, were also capable of inducing an LH surge in rats pretreated with PCPA. The serotonin reuptake blocker chlorimipramine was ineffective in stimulating LH release in PCPA blocked animals. Another reuptake blocker, zimelidine was only partially effective in this regard. These two reuptake blockers, as well as amitriptyline, when injected to non-PCPA treated rats led to the reduction or inhibition of the expected LH surge. Four serotonin receptor antagonists, cyproheptadine, methysergide, cinanserin and SQ-10,631, were each able to reduce or abolish the progesterone induced surge of LH. These results suggest that some of the reuptake blockers of serotonin are also capable of inhibiting receptor binding for this neurotransmitter and strongly indicate that serotonin has a stimulatory role in the steroid induced release of LH in castrated rats.