Effects of Gonadal Steroids on the Growth of Human Pituitary Adenomas in vitro

Abstract

The effects of testosterone (T), dihydrotestosterone (DHT) and methyltrienolone (R 1881) on cell proliferation of eight human pituitary tumors in culture wre assessed by [³H]thy-midine incorporation and compared to those of progesterone (Pg) and 17β-estradiol. Receptors for androgens (AR), estrogens (ER) and progesterone (PgR) were characterized. AR had a significant inhibitory effect on all AR-positive tumors, whatever their hormonal content. Inhibitory effects of either T and DHT < R1881 < Pg were observed in tumors co-expressing AR and PgR. The inhibitory effect of R 1881 on a PgR-posi-tive/AR-negative tumor suggested that R 1881 action was partially PgR-mediated. The effects of either T or the nonaromatizable DHT and R 1881 were unrelated to ER expression. We conclude that AR can modulate the growth of human pituitary tumors through direct receptor-mediated intracellular pathways which may be common to various pituitary cell types.

Immunoexpression of Androgen Receptor in the Nontumorous Pituitary and in Adenomas

“…With respect to pituitary tumors, our study expanded upon the limited, published data referred to in the introduction [16][17][18][19]. We found gonadotroph and null cell and corticotroph adenomas to show higher frequencies of AR positivity than did other adenoma types.…”

“…6 Corticotroph adenoma. Note the AR immunoreactivity in this rather frequently immunoreactive adenoma variant Nonetheless, in vitro effects of androgens upon adenoma cell growth have been studied in a serum-free medium [18]; the authors demonstrated enhanced growth of both gonadotroph and prolactin cell adenomas.…”

“…In brain, they are found mainly in hypothalamic neurons but also at other sites (Tables 1 and 2). A variety of animal studies have established the precise distribution of ARs in the hypothalamus and pituitary; these are summarized in Tables 1 and 2. In human neoplasms, ARs have been identified in carcinomas of prostate [11], breast [17,18], ovary [12], and endometrium [13,14], as well as in meningiomas [15] and in pituitary adenomas [16][17][18][19][20]. All but one of the latter studies, a limited immunohistochemical examination [19], was biochemical in nature.…”

The Role of Aryl Hydrocarbon Receptor (AHR) and AHR-Interacting Protein (AIP) in the Pathogenesis of Pituitary Adenomas

“…Studies from our laboratory have shown that PA express sex steroid hormones receptors with a differential pattern according to phenotype and patient's gender and gonadal function (Jaffrain-Rea et al 1996 ) , and that sex steroids are able to modulate their proliferation in vitro accordingly (Caronti et al 1995 ) . In particular, ER expression was higher in male prolactinomas and 17 b -estradiol had a proliferative effect on most ER-expressing PA.…”

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL)

“…The intensity of fluorescence of the sample was compared to an intensity scale obtained by serial dilutions of a goat anti-mouse IgG F(ab),-FITC. In order to verify whether increased elastin production by pathological fibroblasts could result from enhanced cell proliferation, in vitro [3H]-thymidine incorporation by both normal and pathological cells was evaluated at days 1, 2, 3, 6 of culture in complete medium, as previously described (23). The test was carried out in triplicate on each culture and results were expressed as mean count per minute (mean c.p.m.).…”