CELLULAR MECHANISMS OF ESTROGEN-INDUCED AND DOPAMINE-INDUCED CONTROL OF GLANDULAR KALLIKREIN IN THE ANTERIOR-PITUITARY OF THE RAT

Glandular kallikrein (GK, a trypsin-like serine protease) exhibits est rogen induction and dopamine repression in rat pituitary lactotrophs. Steroid induction may reflect primary actions to increase selectively the synthesis of specific proteins, or may be part of broad cellular r esponses secondary to steroid-induced phenotype transitions. This stud y examined the cellular mechanisms underlying estrogen and dopaminergi c control of lactotroph GK using a quantified immunocytochemical appro ach. Pituitaries from ovariectomized rats exhibited little GK staining . Estradiol treatment for 10 days produced dose-dependent increases in pituitary mass, the percentage of lactotrophs (indicating lactotroph proliferation) and the percentage of GK-positive cells. Also, GK stain ing intensity was dependent upon estradiol dose, increasing 4-fold bet ween 5 mu g and 50 mu g/48 h. Dopamine receptor blockade with haloperi dol (2.5 mg/kg/24 h) elicited weak GK immunostaining in 46% of the lac totrophs in the absence of estradiol, and markedly potentiated GK stai ning intensity elicited with low but not high doses of estradiol. The results suggest that GK induction is a primary estrogen effect, and is not secondary to a phenotype transition: the induction is enhanced by estrogen-induced lactotroph proliferation. Dopaminergic systems stron gly inhibit GK induction by low estradiol levels. This dopaminergic mo dulation may shift the induction of lactotroph GK to physiological eve nts associated with high estradiol levels or low dopaminergic tone.