CALCITONIN INHIBITS TESTOSTERONE AND LUTEINIZING-HORMONE SECRETION THROUGH A MECHANISM INVOLVING AN INCREASE IN CAMP PRODUCTION IN RATS

Effects of calcitonin peptides, including human calcitonin (hCT), salm on calcitonin (sCT), and calcitonin gene-related peptide (CGRP), on th e secretion of testosterone and luteinizing hormone (LH) in male rats were studied. Male rats were injected intravenously with human chorion ic gonadotropin (hCG), calcitonin peptides, or hCG plus calcitonin pep tides. Blood samples were collected at several intervals following hor mone challenge. In an in vitro experiment, testis blocks were incubate d with hCG (0, 0.05, 0.5, or 5 IU/ml) or hCG (0.5 IU/ml) plus calciton in peptides (0-10(-9) or 10(-6) M) at 34 degrees C for 30 minutes, Bot h medium and plasma samples were extracted by ether and analyzed for t estosterone by radioimmunoassay (RIA). The concentration of calcium in each plasma sample was measured by an automatic calcium analyzer. The anterior pituitary gland (AP) was incubated with or without calcitoni n peptides (0-10 nM) at 37 degrees C for 30 minutes. They were then in cubated with gonadotropin releasing hormone (GnRH, 10 nM) for a furthe r 30 minutes. The concentration of LH in AP medium was measured by RIA . The accumulation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in both testicular tissues and APs wer e measured by RIA. A single intravenous injection of calcitonin peptid es decreased the basal and hCG-stimulated levels of plasma testosteron e gradually from 60 to 180 or 360 minutes after challenge. The plasma calcium was not altered by the injection of calcitonin peptides and/or hCG. Administration of calcitonin peptides in vitro resulted in a dos e-dependent inhibition of both basal and hCG-stimuiated release of tes tosterone. Meanwhile, calcitonin peptides caused a dose-dependent inhi bition of the basal release of LH in vitro from rat APs. The content o f cAMP in both testes and APs was increased by all calcitonin peptides . Neither hCT nor sCT altered the content of cGMP in testes and APs, T hese results suggest that calcitonin peptides, including hCT, sCT, and CGRP, inhibit the spontaneous and gonadotropin-stimulated secretion o f testosterone by acting directly at testes and reducing the release o f pituitary LH through a mechanism involving an increase in cAMP produ ction.