Detection of the alpha-subunit of inhibin in trophoblastic neoplasia

Pelkey, Timothy J.; Frierson, Henry F.; Mills, Stacey E.; Stoler, Mark H.

doi:10.1016/s0046-8177(99)90296-4

Cited by 62 publications

(57 citation statements)

References 53 publications

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“…Our extended data support this, since positive staining was seen in all adenomas studied, indicating that loss of expression is not an early event in tumorigenesis. This pattern was seen in two of the other three published studies (Chivite et al 1998, McCluggage et al 1998 but Pelkey et al (1998) found 5 of 23 adenomas immunonegative. The reasons for these differences are unclear.…”

Section: Discussionmentioning

confidence: 62%

“…The observation that the same pattern of tumour development occurred in mice bearing a SV40 T-antigen transgene, driven by the inhibin promoter (Kananen et al 1996), indicates physiological activation of the promoter for the inhibin subunit gene in the adrenal gland, which leads to the immortalisation of cells by expression of the SV-40 T antigen. In addition, there is evidence that, in the human, adrenocortical adenomas secrete inhibin-like immunoreactive material (Nishi et al 1995) and that both adenomas and carcinomas immunostain positively for inhibin (Chivite et al 1998, McCluggage et al 1998, Munro et al 1998, Pelkey et al 1998. This would suggest that inhibin is not a tumour suppressor for the adrenal cortex in man.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, mice bearing an inhibin promoter, Simian virus 40 T (SV40 T)-antigen fusion gene, show the same pattern of tumour development (Kananen et al 1996). Secretion of inhibin immunoreactive material from human tumours has been reported as has immunopositivity for inhibin (Chivite et al 1998, McCluggage et al 1998, Munro et al 1998, Pelkey et al 1998. Whether this reflects free subunits or mature inhibin, as outlined above, is unclear, but immunopositivity for subunits on tissue sections (Munro et al 1998) indicates the potential for producing the mature dimers.…”

Section: Introductionmentioning

confidence: 99%

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The expression of inhibin/activin subunits in the human adrenal cortex and its tumours

Munro

Kennedy²,

McNicol³

1999

Journal of Endocrinology

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Inhibins and activins are dimeric proteins of the transforming growth factor-superfamily which have been shown to be expressed in the adrenal cortex. Recent studies have suggested a role for these peptides in the pathogenesis and/or function of adrenal tumours. To investigate further their physiological and pathological roles, we have documented immunoreactivity for inhibin , A and B subunits in normal adult and fetal human adrenals, in hyperplastic adrenals and in adrenal tumours.In the normal and hyperplastic adult gland, diffuse immunopositivity was demonstrated for subunits, suggesting that activins ( dimers) can be expressed in all zones. Inhibin was limited to the zona reticularis and the innermost zona fasciculata in the normal gland, extending centripetally into the zona fasciculata in hyperplasia, supporting a role for ACTH in the regulation of expression, and suggesting that expression of inhibins ( dimers) is restricted.Immunopositivity for all three subunits was seen in both fetal and definitive zones of the fetal cortex, indicating that both inhibins and activins could be expressed in both.Immunopositivity for all three subunits was seen in most adrenocortical tumours. Loss of immunopositivity for inhibin in a subgroup of carcinomas might indicate a role in tumour progression. The greater intensity of staining for inhibin in tumours associated with Cushing's syndrome again suggests a link with cortisol production.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The expression of inhibin/activin subunits in the human adrenal cortex and its tumours

Munro

Kennedy²,

McNicol³

1999

Journal of Endocrinology

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“…Most of the Cushing's tumours showed fairly strong immunostaining, although the mRNA expression was basically at the same level as in normal adrenals. Pelkey et al (1998) also presented strong immunohistochemical staining of inhibin in Cushing's and virilizing adrenocortical tumours. Very high expression of inhibin in zona reticularis and in virilizing tumours supports a role of inhibin in androgen production.…”

Section: Discussionmentioning

confidence: 87%

“…Recently two papers reported immunoreactivity against inhibin in adrenocortical tumours (Chivite et al 1998, McCluggage et al 1998. Further studies discovered a considerable number of adrenocortical tumours exhibiting no immunostaining for inhibin (Pelkey et al 1998, Renshaw & Granter 1998.…”

Section: Introductionmentioning

confidence: 99%

Expression of inhibin alpha in adrenocortical tumours reflects the hormonal status of the neoplasm

Arola

Liu²,

Heikkilä³

et al. 2000

Journal of Endocrinology

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Inhibins are gonadal glycoprotein hormones whose main endocrine function is to inhibit pituitary FSH secretion. In addition to testes and ovaries, other steroid-producing organs are sites of inhibin subunit expression. To study the role of inhibins in human adrenal gland, we screened a panel of 150 adrenals (10 normal adrenals, 25 adrenocortical hyperplasias, 65 adrenocortical adenomas, 30 adrenocortical carcinomas and 20 phaeochromocytomas) for inhibin expression. mRNA levels of inhibin subunit were studied in 57 samples and all tissues were stained immunohistochemically with an inhibin subunit-specific antibody. Inhibin mRNA was detected in all adrenocortical tissues. Virilizing adenomas possessed a 10-fold higher median inhibin mRNA expression than did normal adrenals. Bilaterally and nodularly hyperplastic adrenals and other than virilizing adrenocortical tumours had their median inhibin mRNA levels close to those of normal adrenals. Immunohistochemically, inhibin subunit was detectable in all normal and hyperplastic adrenals, as well as in 73% of the adrenocortical tumours. However Our data show that inhibin subunit is highly expressed in both normal and neoplastic androgenproducing adrenocortical cells, with less expression in cortisol-producing and hardly any in aldosteroneproducing cells. This suggests a specific role for inhibins in the regulation of adrenal androgen production. We did not find any significant difference in inhibin expression between benign and malignant adrenocortical tumours. Thus inhibin gene does not seem to have a tumour suppressor role in human adrenal cortex.

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Serum activin A and inhibin A

Florio

Severi

Cobellis

et al. 2002

Cancer

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BACKGROUND Although human placenta is a well established, rich source of proteins, hCG is the only measurement available to date in diagnosing the occurrence of the hydatidiform mole. Serum levels of a new placental protein, immunoreactive inhibin, were high in molar pregnancy, but the inhibin assay never became of clinical use, due to its low specificity and reliability. Since specific assays are now available for inhibin A, inhibin B, and activin A, the current study evaluated whether and which of these placental proteins is increased in presence of a molar pregnancy. METHODS Serum inhibin A, inhibin B, activin A, and hCG levels were assayed in: A) 6 women with molar pregnancies, before and after evacuation; B) 37 healthy pregnant women; and C) 22 healthy nonpregnant women. RESULTS Women with partial hydatidiform moles had significantly higher serum levels of inhibin A (P < 0.001) and activin A (P < 0.001) than healthy pregnant women, several fold higher than the 95% confidence interval of control values. After evacuation, the levels of both inhibin A (P < 0.001) and activin A (P < 0.05) declined significantly to the levels of nonpregnant controls. Molar hCG concentrations were significantly higher than in normal pregnancy (P < 0.001), but some values within the 95% confidence interval of normal values. Despite a significant decrease (P < 0.05) after evacuation, hCG levels were still higher than in nonpregnant women. CONCLUSIONS The present data strongly suggest that serum inhibin A and activin A measurement may be of value in diagnosis and short‐term follow‐up of molar pregnancy. Cancer 2002;94:2618–22. © 2002 American Cancer Society. DOI 10.1002/cncr.10524

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Detection of the alpha-subunit of inhibin in trophoblastic neoplasia

Cited by 62 publications

References 53 publications

The expression of inhibin/activin subunits in the human adrenal cortex and its tumours

The expression of inhibin/activin subunits in the human adrenal cortex and its tumours

Expression of inhibin alpha in adrenocortical tumours reflects the hormonal status of the neoplasm

Serum activin A and inhibin A

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