<i>In vitro</i> secretion of FSH by cultured clinically nonfunctioning and gonadotroph pituitary adenomas is directly correlated with locally produced levels of activin A

Wessels, H. T.; Hofland, Leo J.; Wal, Ronald van der; Gastel, L. Van; Koetsveld, Peter M. van; Herder, Wouter W. de; Jong, Frank H. de

doi:10.1046/j.1365-2265.2001.01194.x

Cited by 6 publications

(4 citation statements)

References 45 publications

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“…Kwekkeboom et al (10) reported no correlation between the amounts of LH and FSH released in vitro and the serum hormone values in 20 patients with NFPAs, but LH and FSH were released in only seven and nine cultures respectively of the 20 tumours studied, making correlations difficult to interpret. We were able to compare data from 38 subjects and found no correlation for LH but did demonstrate a significant correlation for FSH, as has been shown previously by Wessels et al (18) in a small study of patients with gonadotrophinomas (n ¼ 4) and NFPAs (n ¼ 14). This positive correlation between serum and media FSH suggests that the cultures are reflecting the in vivo situation as far as FSH secretion is involved.…”

Section: Discussionsupporting

confidence: 61%

“…At the pituitary level, activin acts in a local manner to stimulate FSH expression and secretion and has an antiproliferative effect, with these actions being blocked by follistatin and inhibin (21). A positive correlation has been demonstrated in NFPAs between activin and FSH by two groups (17,18). Other studies have shown that the antiproliferative effect of activin may be lost in some gonadotrophinomas (22).…”

Section: Discussionmentioning

confidence: 89%

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FSH secretion predominates in vivo and in vitro in patients with non-functioning pituitary adenomas

Hanson

Aylwin²,

Monson³

et al. 2005

eur j endocrinol

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Objective: Non-functioning pituitary adenomas (NFPAs) are characterised by the lack of symptoms of hormone hypersecretory syndromes but in vitro studies have demonstrated that tumour cells may stain for gonadotrophins and/or their a-or b-subunits. In this study, we aimed to examine the pattern of secretion of LH and FSH from a series of pituitary adenomas cultured in vitro and where data were available to relate the results to pre-operative serum gonadotrophin levels. Methods: The in vitro secretion of LH and FSH was measured from 46 cultured NFPAs and compared with pre-operative serum gonadotrophin levels in 38 patients. Peri-tumorous 'normal' pituitary cell cultures from 20 additional pituitary tumour patients were used for comparison with the NFPA group. Results: A median pre-operative LH:FSH ratio of 0.33:1 was found in 38 patients with NFPAs. Preferential secretion of FSH was also documented from media of 46 NFPAs cultured in vitro with a median LH:FSH ratio of 0.32:1. A significant correlation (r ¼ 0.43, P , 0.01) was observed between serum and media levels of FSH but not LH. Peri-tumorous 'normal' pituitary cells released LH and FSH in a reversed ratio (median LH:FSH ratio ¼ 3.6:1, P , 0.01 compared with NFPAs). Conclusions: This study has evaluated pre-operative serum gonadotrophin levels and in vitro release of hormones in cultures of surgically removed tissue from patients with NFPAs. The data suggest preferential secretion of FSH occurs both in vitro and in vivo. By demonstrating that NFPAs cultured in vitro reflect the in vivo situation of preferential secretion of FSH, it may be possible in future to perform functional studies using this system to elucidate the cellular and molecular mechanisms involved in the development of an imbalance in gonadotroph cells preferentially overproducing FSH in NFPAs.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 89%

FSH secretion predominates in vivo and in vitro in patients with non-functioning pituitary adenomas

Hanson

Aylwin²,

Monson³

et al. 2005

eur j endocrinol

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“…Transforming growth factor-a (TGF-a), epidermal growth factor (EGF), and their common tyrosin kinase receptor (EGF-R) are overexpressed in pituitary adenomas, particularly in those with high aggressiveness (32)(33)(34)(35). Moreover, in gonadotroph adenomas activin/inhibin subunits appear highly expressed together with the specific type I and type II receptors while follistatin, which prevents activin action by binding this subunit, is reduced (36)(37)(38). Among the members of the fibroblast growth factor (FGF) and receptor family, particular attention has been paid to FGF-2 and FGF-4, both showing mitogenic and angiogenic activity (4,(39)(40)(41)(42).…”

Section: Genetics Of Pituitarytumorsmentioning

confidence: 99%

Genetics of Pituitary Tumors: Focus on G-Protein Mutations

Lania

Mantovani

Spada

2003

Exp Biol Med (Maywood)

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In recent years the demonstration that human pituitary adenomas are monoclonal in origin has provided further evidence that pituitary neoplasia arise from the replication of a single mutated cell in which growth advantage results from either activation of proto-oncogenes or inactivation of tumor suppressor genes. While common oncogenes, such as Ras, are only exceptionally involved, the only mutations identified in a significant proportion of pituitary tumors, and particular in GH-secreting adenomas, occur in the Gsalpha gene (GNAS1) and cause constitutive activation of the cAMP pathway (gsp oncogene). Moreover, pituitary tumors overexpress hypothalamic releasing hormones, growth factors, and their receptors as well as cyclins involved in cell cycle progression. As far as the role of tumor suppressor genes in pituitary tumorigenesis is concerned, reduced expression of these genes seems to frequently occur in pituitary tumors as a consequence of abnormal methylation processes. Although the only mutational change so far identified in pituitary tumors is the gsp oncogene, this oncogene is not associated with a clear phenotype in patients bearing positive tumors. Mechanisms able to counteract the cAMP pathway, such as high sensitivity to somatostatin, and induction of genes with opposite actions, such as phosphodiesterases, CREB end ICER, or instability of mutant Gsalpha, have been proposed to account for the lack of genotype/phenotype relationships.

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“…Moreover, gonadotrope cells produce follistatin, a TGF-β ligand that binds activin and blocks activin actions. In pituitary tumors, activin receptors are highly expressed while follistatin is reduced [50, 51]. Accordingly, it has been proposed that the imbalanced expression of these proteins, resulting in an enhanced activin signaling, may represent a pathogenetic mechanism in the development of this adenoma subtype.…”

Section: Signaling Of Growth Factors In the Pathogenesis Of Pituitarymentioning

confidence: 99%

Hormonal Signaling and Pituitary Adenomas

Spada¹,

Lania²,

Mantovani³

2007

Neuroendocrinology

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In recent years the demonstration that human pituitary adenomas are monoclonal in origin provides further evidence that pituitary neoplasia arise from the replication of a single mutated cell in which growth advantage results from either activation of proto-oncogenes or inactivation of tumor suppressor genes. Mutations in common oncogenes and tumor suppressor genes are only exceptionally involved in pituitary tumors. Since pituicytes may proliferate in response to hypothalamic neurohormones, locally produced growth factors and peripheral hormones, it has been speculated that dysregulation of the signaling molecules that constitute these pathways may confer growth advantage to the target cell, finally resulting in tumor formation. The only mutational change so far recognized to be unequivocally associated with pituitary tumors occur in the Gsα gene (GNAS1) and cause constitutive activation of the cAMP-dependent pathway. However, other components of pituitary-specific pathways are frequently altered in their expression and activity. This review will focus on the possible impact of G proteins and other components of hormone signaling on pituitary tumorigenesis.

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In vitro secretion of FSH by cultured clinically nonfunctioning and gonadotroph pituitary adenomas is directly correlated with locally produced levels of activin A

Abstract: It is concluded that levels of activin A, follistatin and FSH in media of cultured nonfunctioning adenomas and gonadotroph adenomas are positively correlated. This suggests that these adenomas secrete FSH in response to the relatively high locally produced levels of activin A.

Cited by 6 publications

References 45 publications

FSH secretion predominates in vivo and in vitro in patients with non-functioning pituitary adenomas

FSH secretion predominates in vivo and in vitro in patients with non-functioning pituitary adenomas

Genetics of Pituitary Tumors: Focus on G-Protein Mutations

Hormonal Signaling and Pituitary Adenomas

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