The effects of the cholecystokinin antagonist, proglumide, on gonadotropin release in the rat.

Since cholecystokinin had manifest effects on anterior pituitary hormone secretion following its intraventricular injection in ovariectomized rats, we have evaluated the effects of the cholecystokinin antagonist, proglumide, to assess the physiologic significance of CCK in the control of gonadotropin secretion. Conscious rats of either sex were used following implantation of third ventricular and/or intravenous cannulae for the administration of proglumide. Blood samples were drawn from conscious animals at various times after the injection of the compound. In castrate female rats proglumide produced a small but significant increase in plasma LH whether administered by the intravenous or intraventricular route at the lower dose of 10 or 2 micrograms, respectively. The higher doses of 10 micrograms injected intraventricularly or 100 micrograms, injected intravenously failed to affect LH levels in these animals. In contrast there was a much larger increase in plasma LH in castrate males following intraventricular or intravenous injection of the lower doses of proglumide. Even after the higher doses, there was a slight increase in levels of LH by either route of injection. The results indicate that in the castrate animal proglumide can elevate LH levels by either route of injection but that the response is greater in castrate males than females. The reduction in response with the higher doses may reflect an agonist activity of proglumide. By contrast proglumide had no effect on plasma FSH except for a slight elevation observed following the intravenous or intraventricular injection of the lower doses of the compound in castrate males. The results favor a physiologically significant role of CCK in control of LH release in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)