Pituitary Aromatase P450 May Be Involved in Maintenance of the Population of Luteinizing Hormone-Positive Pituitary Cells in Mice

Abstract

As aromatase P450 is located in several pituitary cells, testosterone can be transformed into 17β-estradiol in the gland by the enzyme. The possible role of this transformation in pituitary function remains to be elucidated, but some evidence suggests a physiological and pathophysiological role for pituitary aromatase. To determine its relevance in the modulation of pituitary function, mainly associated with reproduction, luteinizing hormone (LH)-positive cells in the hypophysis of female and male aromatase knockout (ArKO) mice were studied. In all LH-positive cells, significant increases in the cellular (p < 0.01) and nuclear (p < 0.05) areas were found in the ArKO mice compared to the wild-type mice. In the ArKO mice, LH-positive cells were more abundant (p < 0.01); they were characterized by a stronger cytoplasmic reaction and the cells were more polygonal and exhibited more short, thick cytoplasmic prolongations than those in the wild-type mice. Moreover, LH-positive cells showed a greater proliferation rate in the ArKO mice compared to the wild-type mice (p < 0.01). These findings suggest that the local production of estradiol mediated by pituitary aromatase is necessary for the regulation of LH-positive gonadotropic cells, exerting an autoparacrine inhibitory regulation. These results could underlie the higher pituitary aromatase expression observed in male versus female mice. Similar effects were found in ArKO male and female mice, suggesting that in both sexes the effects of estrogens on maintenance of the LH-positive pituitary cell population could be related to the local aromatization of testosterone to estradiol inside the hypophysis. Therefore, aromatase could modulate pituitary LH-positive cells in males through local estradiol synthesis.

A 5α‐reductase (SRD5A2) polymorphism is associated with serum testosterone and sex hormone–binding globulin in men, while aromatase (CYP19A1) polymorphisms are associated with oestradiol and luteinizing hormone reciprocally

“…Hence, the feedback effects of T on the male gonadal axis may be driven to some extent via conversion of T to E2 within the hypothalamus and/or pituitary. The proportion of pituitary cells showing immunostaining for LH was greater in aromatase knockout compared to wild‐type mice, consistent with a role for local production of E2 in regulation of pituitary LH synthesis . In our multivariate analysis involving the cohort as a whole, circulating E2 was not associated with serum LH.…”

“…The proportion of pituitary cells showing immunostaining for LH was greater in aromatase knockout compared to wild-type mice, consistent with a role for local production of E2 in regulation of pituitary LH synthesis. 35 In our multivariate analysis involving the cohort as a whole, circulating E2 was not associated with serum LH. In men aged <65 years, serum E2 was positively associated with LH, rather than inversely which would be expected for a negative feedback loop.…”

A compromised gsdf signaling leads to gamatogenesis confusion and subfertility in medaka

“…No apparent differences in the expression of cyp19b have been observed between males and females in zebrafish(Kallivretaki et al, 2007), but a sexually dimorphic expression after puberty has been found in medaka brain(Okubo et al, 2011), indicating that cyp19b is involved in HPG regulation of gonadal development at the onset of spermatogenesis. The expression of both cyp19b and lh decreased in Sissy pituitaries, in agreement with the findings in mice aromatase knockout (ArKO), indicating that aromatase is involved in maintaining the Lh-positive cells in medaka and mouse pituitary(Carretero et al, 2016).…”

Relation among Aromatase P450 and Tumoral Growth in Human Prolactinomas

“…By means of immunohistochemistry, Western blotting, and in situ hybridization, it has been demonstrated that gonadal steroids play an important role in the expression of aromatase in the pituitary gland of adult rats. Moreover, treatment with aromatase inhibitors induces morphometric alterations and changes in the cellular proliferation of some glandular pituitary cells and similar changes can be observed in lactotroph cells or LH-positive gonadotroph cells in knock-out mice for aromatase [ 40 , 41 ].…”