Regulation of adenohypophyseal pyroglutamyl aminopeptidase II activity by thyrotropin-releasing hormone and phorbol esters.

Thyrotropin-releasing hormone (TRH) is inactivated by a narrow specificity ectopeptidase, pyroglutamyl aminopeptidase II (PPII), in the proximity of target cells. In adenohypophysis, PPII is present on lactotrophs. Its activity is regulated by thyroid hormones and 17beta-estradiol. Studies with female rat adenohypophyseal cell cultures treated with 3,3',5'-triiodo-L-thyronine (T3) showed that hypothalamic/paracrine factors, including TRH, can also regulate PPII activity. Some of the transduction pathways involve protein kinase C (PKC) and cyclic adenosine monophosphate (cAMP). The purpose of this study was to determine whether T3 levels or gender of animals used to propagate the culture determine the effects of TRH or PKC. PPII activity was lower in cultures from male rats. In cultures from both sexes, T3 induced the activity. The percentages of decrease due to TRH or PKC were independent of T3 or gender; the percentage of decrease due to cAMP may also be independent of gender. These results suggest that T3 and hypothalamic/paracrine factors may independently control PPII activity in adenohypophysis, in either male or female animals.