Inhibition of thein VitroPituitary Response to Luteinizing Hormone-Releasing Hormone by Melatonin, Serotonin, and 5-Methoxytryptamine1

Abstract
The effects of pineal indole compounds on the response of the neonatal rat anterior pituitary gland to LH[luteinizing hormone]-releasing hormone (LHRH) were studied in organ culture. After 24 h of culture under control conditions, pituitary glands from 5 day old female rats were routinely incubated for an additional 24 h with the test compounds. Medium LH content was determined by double antibody radioimmunoassay. LHRH (10-9M) induced a 10-fold increase in LH levels over control values. Melatonin at a concentration of 10-9M significantly reduced the LHRH-stimulated release of LH; maximal suppression to 14% was attained with 10-8M melatonin. Similarly, 10-8M LHRH caused a 26-fold elevation in medium LH which was suppressed to 62, 55 and 47% by 10-9, 10-8 and 10-7M melatonin, respectively. In short-term experiments, inhibition was evident within 30 min of treatment. A developmental study of the effect of melatonin on LH release revealed significant inhibition with pituitary glands from rats 2, 5 and 10 days of age but not with glands from animals 21 and 30 days of age. Other pineal indoles were tested for their effects on the LH response to a single dose of LHRH (3 .times. 10-10M). Serotonin at a concentration of 10-9M significantly suppressed LH release; maximal reduction to 37-53% occurred with 10-8 to 10-6M serotonin. 5-Methoxytryptamine also produced an inhibition which was significant only at 10-6M, the highest concentration tested. N-Acetylserotonin, 5-hydroxyindoleacetic acid, 5-methoxyindoleacetic acid, 5-hydroxytryptophol and 50-methoxytryptophol showed no consistent inhibitory activity at doses up to 10-7M. Melatonin, serotonin and 5-methoxytryptamine can probably act directly on the neonatal pituitary gland to suppress LHRH-induced release of LH.