Activin and inhibin in the human adrenal gland. Regulation and differential effects in fetal and adult cells.

Spencer, Susan J.; Rabinovici, Jaron; Mesiano, Sam; Goldsmith, Paul C.; Jaffe, Robert B.

doi:10.1172/jci115827

Cited by 109 publications

(105 citation statements)

References 39 publications

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“…Although in early studies zona glomerulosa was suggested to be immunohistochemically positive for inhibin (Spencer et al 1992), most recent studies have suggested an inner zonespecific staining pattern (McCluggage et al 1998). We also showed negative inhibin immunostaining in the zona glomerulosa, weak staining in the zona fasciculata, and very strong staining in the zona reticularis.…”

Section: Discussionsupporting

confidence: 52%

“…Both inhibin and subunit mRNA species and peptides can be detected in adrenal cortex, but not in the medulla (Meunier et al 1988, Voutilainen et al 1991, Spencer et al 1992, McCluggage et al 1998. The first reports suggested all adrenocortical tumours to be inhibin positive (Chivite et al 1998, McCluggage et al 1998.…”

Section: Discussionmentioning

confidence: 99%

“…Steroid-producing organs, pituitary gland, placenta and the central nervous system are the main sites of inhibin subunit gene expression (Meunier et al 1988, Voutilainen 1995. In humans, inhibin subunit gene is expressed in both foetal and adult adrenal cortex (Voutilainen et al 1991, Spencer et al 1992, and the inner zones, particularly the zona reticularis, have the strongest immunoreactivity with anti-inhibin antibody (Chivite et al 1998, McCluggage et al 1998. The role of adrenal inhibins is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Inhibin mRNA has been demonstrated in the ovine (Crawford et al 1987) and human (Voutilainen et al 1991) adrenal cortex and its expression has been shown to be upregulated by adrenocorticotrophic hormone (ACTH). Immunopositivity for inhibin has been reported in the rat (Merchenthaler et al 1991) and human (Spencer et al 1992) adrenal cortex. There is less information on the expression of subunits.…”

Section: Introductionmentioning

confidence: 99%

“…Plasma immunoreactive inhibin levels are higher in the adrenal veins than in vena cava or the peripheral circulation (Nishi et al 1995) and normal adrenocortical cells in culture secrete inhibin-like immunoreactive material (Haji et al 1991, Spencer et al 1992. While this may reflect production of mature inhibin dimer it may also indicate the presence of free subunit which may crossreact in the assay.…”

Section: Introductionmentioning

confidence: 99%

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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Anti-?-inhibin

Fetsch

Powers

Zakowski

et al. 1999

Cancer

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Activin and inhibin in the human adrenal gland. Regulation and differential effects in fetal and adult cells.

Cited by 109 publications

References 39 publications

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

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

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

Anti-?-inhibin

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