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.
Highlights
Aromatase P450 is a complex protein belonging to family 19 of the P450 superfamily of enzymes, termed CYP19
It is found throughout the phylum vertebrates and formed by two components, cytochrome P450 and nicotinamide adenine dinucleotide phosphate (NADPH) cytochrome P450 reductase, located in the membranes of the endoplasmic reticulum; the human gene is unique compared to the rest of the other members of this superfamily [1,2]
The treatment of male rats with aromatase inhibitors elicits a decrease in the activity and proliferation of lactotroph cells [41], and similar findings can be observed in aromatase knock out (KO) mice [73]
Summary
Aromatase P450 is a complex protein belonging to family 19 of the P450 superfamily of enzymes, termed CYP19. Studies in animals and humans have demonstrated that estrogen stimulates pituitary tumor transforming gene (PTTG) expression [27]. This gene, the first proto-oncogene to be identified, is weakly expressed in normal tissues. It is widely detected in malignant cell lines and in most pituitary tumors [28,29]; estrogens are one of the factors involved in the pathogenesis of prolactinoma. The under-expressed genes UGT2B7, Let, and miR-493 are primarily involved with steroid metabolism and cell cycle regulation, which may contribute directly to the formation and progression of prolactinomas [23]
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