Basic fibroblastic growth factor stimulates prolactin secretion from human anterior pituitary adenomas without affecting adenoma cell proliferation.

Abstract The process of angiogenesis occurs in many physiological states, but it is also essential for the growth of solid tumours and metastasis formation. An abnormal arterial vascularization has been shown in prolactin-secreting pituitary adenomas induced by prolonged treatment with oestrogens in Fischer 344 (F344) rats. It is thought that anti-angiogenic agents might be useful in therapy for these tumours. Fumagillin and its analogue TNP-470 are known to inhibit endothelial cell proliferation selectively, but their effect on lactotroph cell secretory function and prolactinoma formation has not yet been described. The aim of the present study was to examine the effects of fumagillin and TNP-470 on prolactin secretion, and morphological and vascular changes within the anterior pituitary in long-term oestrogen-treated male F344 rats in vivo and in vitro. As expected, 7 weeks after s.c. implantation of Silastic tubes containing 10 mg diethylstilboestrol (DES), a very high rise in serum prolactin levels was found. Both angiogenesis inhibitors injected s.c. at doses of 10 mg/kg body weight for 24 days attenuated the stimulatory effect of DES on prolactin production and release. They also diminished prolactin cell density and inhibited cell proliferation expressed as the number of anterior pituitary cells labelled with bromodeoxyuridine (BrdU), but the effect of TNP-470 was minor compared with fumagillin. Both angioinhibitors suppressed neovascularization within the anterior pituitary with similar potency but, on the other hand, they did not affect DES-induced increases in prolactin secretion from cultured rat pituitary cells and cell proliferation in vitro. In conclusion, our results provide strong evidence for the anti-tumour and anti-prolactin activity of angiogenesis inhibitors in the experimentally oestrogen-induced pituitary adenoma; this might be mediated indirectly through the inhibition of angiogenesis. Journal of Endocrinology (1996) 150, 99–106

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17β-Hydroxysteroid Dehydrogenase Type 1, 2, 3, and 4 Expression and Enzyme Activity in Human Anterior Pituitary Adenomas

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.84.4.5619 ◽

1999 ◽

Vol 84 (4) ◽

pp. 1340-1345

Author(s):

V. L. Green ◽

V. Speirs ◽

A. M. Landolt ◽

P. M. Foy ◽

S. L. Atkin

Keyword(s):

Gene Expression ◽

Enzyme Activity ◽

Pituitary Adenomas ◽

Anterior Pituitary ◽

Estrogenic Activity ◽

Hydroxysteroid Dehydrogenase ◽

Messenger Ribonucleic Acid ◽

Human Anterior Pituitary

17β-Hydroxysteroid dehydrogenase (17βHSD) isoforms reversibly catalyze the final step in the formation of estradiol (E2) from estrone (E1) and the formation of testosterone from androstenedione. We have investigated 17βHSD type 1, 2, 3, and 4 gene expression and 17βHSD estrogenic activity in human anterior pituitary adenomas. 17βHSD messenger ribonucleic acid (mRNA) expression was studied by RT-PCR in 42 pituitary tumors and 3 normal pituitaries, 17βHSD activity was studied in 11 tumors and 17βHSD type 1 was immunolocalized in vitro in 6 tumors. 17βHSD type 1 gene expression was detected in 34 of 42 adenomas in all tumor subtypes; 17βHSD type 2 mRNA was detected in 18 of 42 adenomas, but not in prolactinomas; 17βHSD type 3 mRNA was detected in 12 of 42 adenomas, but not in corticotropinomas; 17βHSD type 4 was expressed in 20 of 42 adenomas by all adenoma subtypes. Reversible 17βHSD activity was found in 9 of 11 adenomas, and 17βHSD type 1 immunopositivity was cytoplasmically distributed in all 6 adenomas in vitro. All 4 17βHSD isoforms are variably expressed in human anterior pituitary adenomas, which also show 17βHSD enzyme activity, suggesting that 17βHSD may play an important role in regulating the local cellular levels of estradiol.

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