Pathogenesis of Prolactin-Secreting Pituitary Adenomas

Sherman, B; Schlechte, Janet A.; Halmi, N. S.; Chapler, Frederick K.; Harris, CurtisE.; Duello, TeresaM.; VanGilder, John C.; Granner, DarylK.

doi:10.1016/s0140-6736(78)92339-5

Cited by 94 publications

(14 citation statements)

References 15 publications

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“…However, the risk for development of significant clinical symptoms related to tumor expansion is less than 2% in pregnant women with microadenomas [9]. There appears to be a close association between the use of oral estrogenic contraceptives and the onset of amenorrhea, often accompanied by galactorrhea [25][26][27]. Certain subsets of humans and animals are more sensitive to estrogen's mitogenic properties than the general population [28,29].…”

Section: Estrogen-treated Ratsmentioning

confidence: 99%

Genesis of Prolactinomas: Studies Using Estrogen-Treated Animals

Sarkar

2006

Frontiers of Hormone Research

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Prolactin-secreting adenomas (prolactinomas) are the most prevalent form of pituitary tumors in humans. Our knowledge of the formation of these tumors is limited. Experimental work in animal has uncovered that estradiol exposure leads to prolactinoma formation via orchestrated events involving dopamine D2 receptors, transforming growth factor-β (TGF-β) isoforms and their receptors, as well as factors secondary to TGF-β action. Additionally, these studies determined that TGF-β and b-FGF interact to facilitate the communication between lactotropes and folliculo-stellate cells that is necessary for the mitogenic action of estradiol. The downstream signaling that governs lactotropic cell proliferation involves activation of the MAP kinase p44/42-dependent pathway.Pituitary tumors are primarily adenomas; they account for approximately 10-15% of intracranial tumors. They cause significant morbidity due to local invasion, hypopituitarism or hormone hypersecretion [1,2]. Pituitary tumors are classified as either functioning and secreting excessive amounts of active hormones, or as endocrinologically inactive and secreting no hormones or inactive hormones. Pituitary tumors are also classified by virtue of their size into the arbitrary division of those less than 1 cm as microadenomas and those more than 1 cm as macroadenomas. Pituitary tumors secreting excess prolactin are characterized as prolactinomas. Prolactinomas are the most frequently occurring neoplasm in the human pituitary [3,4]. In the general population, 1:2,800 men and 1:1,050 women are considered to have prolactinomas [5]. In human subjects, prolactinomas occur as both macroadenomas and microadenomas. In addition, mixed growth hormone and prolactin-secreting adenomas are documented to exist in a substantial number of acromegaly patients.Hyperprolactinoma is a condition in which plasma prolactin (PRL) levels are elevated above normal levels. Hyperprolactinemia, with elevation of serum prolactin of more than 200 ng/ml, is characteristically associated with prolactinomas [6]. Hyperprolactinemia causes reproductive dysfunction such as amenorrhea, galactorrhea, and infertility in women [7]. Amenorrhea and galactorrhea may occur alone or together [8]. Up to 25% of patients with secondary amenorrhea have been diagnosed with hyperprolactinemia. Many of these patients showed micro-prolactin adenomas or macro-prolactin adenomas in the pituitary. Although treatments that alter central dopaminergic neuronal functions cause an elevated serum PRL level, in most cases hyperprolactinemia is due to a pituitary tumor. In women, prolactinomas are mainly microadenomas. These microadenomas are rarely associated with hypopituitarism or central nervous system dysfunction. Idiopathic hyperprolactinemia, without demonstrable pituitary or hypothalamic disease, has also been identified. In men, prolactinomas are mainly

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Section: Estrogen-treated Ratsmentioning

confidence: 99%

Genesis of Prolactinomas: Studies Using Estrogen-Treated Animals

Sarkar

2006

Frontiers of Hormone Research

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“…Concern has been raised that male transsexuals treated with high doses of estrogen may have greater risk of hyperprolactinemia and possibly the induction of prolactinoma (Shy et al, 1983;Gooren et al, 1985Gooren et al, , 1988. Also there is increasing concern that the recent apparent increase of hyperprolactinemia in women may be causally related to increased use of estrogens (Sherman et al, 1978;Teperman et al, 1980). It is also known that synthetic as well as endogenous estrogens can increase sex hormone binding globulin (SHBG) binding capacity (Pearlman et aL, 1967;Vermeulen et al, 1969;Dowsett et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

Effect of estrogens on prolactin secretion in transsexual subjects

Goh

Ratnam

1990

Arch Sex Behav

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The effect of estrogens on the secretion of prolactin in 8 different groups of transsexual subjects was studied. Two different types of estrogens, estradiol or its conjugate and ethinyl estradiol, were used. Different doses and durations of exposure were employed. Plasma levels of prolactin and SHBG after estrogen exposure were compared with corresponding levels before treatment. Results showed that for estrogens to exert an enhancing effect on the secretion of prolactin, three factors needed to be considered: (i) the absolute concentration of estrogen, (ii) the duration of exposure, and (iii) whether levels of SHBG are sufficiently altered to change the concentration of free estrogen. It appears that there exist both time and dose thresholds for effective enhancement of prolactin secretion by estrogen. Estradiol and its conjugate are more likely to induce hyperprolactinemia than ethinyl estradiol. The reduced effect of the latter is probably related to its ability to induce large and rapid increases in SHBG binding which probably results in unaltered free estrogen concentration. In the light of this study, treatment of male transsexuals with high doses of estradiol in its conjugate forms must be viewed with caution.

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“…No prolactin cell hyperplasia was found, however, by Sherman etal. (25). It has recently been reported that patients with prolactin-secreting pituitary ade noma may have a defect in the regulation of brain catecholamine metabolism, suggesting that hyperprolactinemia may begin as a primary hypothalamic dis order, and that chronic stimulation of prolactin cells may result in prolactin cell hyperplasia and adenomatous transformation (26).…”

Section: Discussionmentioning

confidence: 99%