Sex-specific regulation of prolactin secretion by pituitary bradykinin receptors

ABELEDO MACHADO, ALEJANDRA INÉS; PEÑA-ZANONI, MILAGROS; BORNANCINI, DANA; CAMILLETTI, MARIA ANDREA; FARAONI, ERIKA YANIL; MARCIAL LÓPEZ, AGUSTINA; RULLI, SUSANA; ALHENC-GELAS, FRANCOIS; DÍAZ-TORGA, GRACIELA

ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2022

0013-7227

Gender differences in the control of prolactin secretion are well documented. Sex-related differences in intra-pituitary factors regulating lactotroph function have recently attracted attention. Gender differences in prolactinoma development are well documented in clinic, prolactinomas being more frequent in women but more aggressive in men, for poorly understood reasons. Kallikrein, the enzyme releasing kinins has been found in the pituitary but there is no information on pituitary kinin receptors and their function. In the present work, we characterized pituitary bradykinin receptors (BRs) at the mRNA and protein levels in two mouse models of prolactinoma, Drd2 receptor gene inactivation and hCGβ gene overexpression, in both males and females, wild type or genomically altered. B2R accounted for 97% or more of total pituitary BRs in both models, regardless of genotype, and was present in lactotrophs, somatotrophs and gonadotrophs. Male pituitaries displayed higher level of B2R than females, regardless of genotype. Pituitary B2R gene expression was downregulated by oestrogen in both males and females but only in females by dopamine. Activation of B1R or B2R by selective pharmacological agonists induced prolactin release in male pituitaries, but inhibited prolactin secretion in female pituitaries. Increased B2R content was observed in pituitaries of mutated animals developing prolactinomas, compared to their respective wild-type controls. The present study documents a novel sex-related difference in the control of prolactin secretion and suggests that kinins are involved, through B2R activation, in lactotroph function and prolactinoma development.