Relation among Aromatase P450 and Tumoral Growth in Human Prolactinomas

Abstract

The pituitary gland is part of hypothalamic-pituitary–gonadal axis, which controls development, reproduction, and aging in humans and animals. In addition, the pituitary gland is regulated mainly by hormones and neurotransmitters released from the hypothalamus and by systemic hormones secreted by target glands. Aromatase P450, the enzyme responsible for the catabolization of aromatizable androgens to estrogens, is expressed in different parts of body, including the pituitary gland. Moreover, aromatase P450 is involved in sexual dimorphism where alteration in the level of aromatase can initiate a number of diseases in both genders. On the other hand, the direct actions of estrogens, mainly estradiol, are well known for stimulating prolactin release. Numerous studies have shown that changes in the levels of estrogens, among other factors, have been implicated in the genesis and development of prolactinoma. The pituitary gland can produce estradiol locally in several types of endocrine cells, and it is possible that aromatase could be responsible for the maintenance of the population of lactotroph cells and the modulation of the action of central or peripheral regulators. Aromatase overexpression due to inappropriate gene regulation has clinical effects such as the pathogenesis of prolactinomas. The present study reports on the synthesis of pituitary aromatase, its regulation by gonadal steroids, and the physiological roles of aromatase on pituitary endocrine cells. The involvement of aromatase in the pathogenesis of pituitary tumors, mainly prolactinomas, through the auto-paracrine production of estradiol is reviewed.

G-protein Coupled Estrogen Receptor Expression in Growth Hormone Secreting and Non-Functioning Adenomas

“…Although the role of estrogen in the genesis of GH-secreting adenomas is less certain, some data suggest locally produced estrogen through aromatization might alter GH synthesis and secretion in both men and women [3,37,38]. Likewise, aromatase expression has been shown in both normal and neoplastic pituitary [3][4][5][6][7]36]. In our study, similar to our [4] and others' [7] previous findings, we detected increased aromatase protein expression in patients with GH-secreting adenoma as compared to those with NFA.…”

“…There is emerging evidence that estrogenic exposure might have a role in the development of different types of pituitary tumors, namely prolactinomas [6,15,36]. Although the role of estrogen in the genesis of GH-secreting adenomas is less certain, some data suggest locally produced estrogen through aromatization might alter GH synthesis and secretion in both men and women [3,37,38].…”

Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens—An Insight From Translational Studies

“…Studies of aromatase overexpression and knockout transgenic mice models confirmed that estradiol is largely responsible for the maintenance of the population of lactotropic cells in males [32,33], apart from playing an essential role in the hypothalamus-pituitary regulation of testicular and associated functions [18,34]. With regard to aromatase expression in pituitary adenomas and its possible association with tumor subtype, sex and/or tumor size, the results are still confounding [29,[35][36][37] and await further multimethodological confirmation and testing. Of note, clinical management of hypogonadism in men with macroprolactinoma, which was refractive to dopamine agonists, required aromatase inhibitor treatment in addition to testosterone replacement, to prevent the secondary rise in PRL and, finally, the potential for tumor enlargement [38].…”

<p>Molecular Mechanisms of Anticancer Activities of Puerarin</p>

“…89 Aromatase P450 is an enzyme that is expressed in different parts of the body, and changes in its level in the body cause different diseases. 90 Different NPs induce apoptosis in cancer cells through the regulation of the JNK pathway. [91][92][93] The oxidative stress generated in SMMC7721 cells with Pue treatment due to ROS causes JNK activation, which causes c-jun inhibition and cell apoptosis.…”