ArticleMolecular and cellular biology2003
Activin induces x-zone apoptosis that inhibits luteinizing hormone-dependent adrenocortical tumor formation in inhibin-deficient mice.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 77 citations in OpenAlex.
- Sexual dimorphism in benign adrenocortical tumours.European journal of endocrinology · 2025Review
- Current insight into the transient X-zone in the adrenal gland cortex.Vitamins and hormones · 2024Review
- Adrenal cortex renewal in health and disease.Nature reviews. Endocrinology · 2021Review
- Construction of a risk signature for adrenocortical carcinoma using immune-related genes.Translational andrology and urology · 2020Article
- Androgen receptor signalling in the male adrenal facilitates X-zone regression, cell turnover and protects against adrenal degeneration during ageing.Scientific reports · 2019Article
- The transient cortical zone in the adrenal gland: the mystery of the adrenal X-zone.The Journal of endocrinology · 2019Review
- Mouse models of adrenocortical tumors.Molecular and cellular endocrinology · 2016Review
- GATA factors in endocrine neoplasia.Molecular and cellular endocrinology · 2016Review
- Toying with fate: Redirecting the differentiation of adrenocortical progenitor cells into gonadal-like tissue.Molecular and cellular endocrinology · 2015Review
- A Novel Population of Inner Cortical Cells in the Adrenal Gland That Displays Sexually Dimorphic Expression of Thyroid Hormone Receptor-β1.Endocrinology · 2015Article
- Adrenocortical zonation, renewal, and remodeling.Frontiers in endocrinology · 2015Review
- Regulation of the adrenocortical stem cell niche: implications for disease.Nature reviews. Endocrinology · 2015Review
- mTOR pathway is activated by PKA in adrenocortical cells and participates in vivo to apoptosis resistance in primary pigmented nodular adrenocortical disease (PPNAD).Human molecular genetics · 2014Article
- Inhibin at 90: from discovery to clinical application, a historical review.Endocrine reviews · 2014Review
- Inhibin alpha-subunit (INHA) expression in adrenocortical cancer is linked to genetic and epigenetic INHA promoter variation.PloS one · 2014Article
- Adrenocortical zonation results from lineage conversion of differentiated zona glomerulosa cells.Developmental cell · 2013Article
- Conditional mutagenesis of Gata6 in SF1-positive cells causes gonadal-like differentiation in the adrenal cortex of mice.Endocrinology · 2013Article
- Animal models of adrenocortical tumorigenesis.Molecular and cellular endocrinology · 2012Article
- The cAMP pathway and the control of adrenocortical development and growth.Molecular and cellular endocrinology · 2012Review
- Adrenocortical stem and progenitor cells: unifying model of two proposed origins.Molecular and cellular endocrinology · 2011Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Inhibin and activin are members of the transforming growth factor beta (TGF-beta) family of ligands produced and secreted primarily by the gonads and adrenals. Inhibin-null (INH(-/-)) mice develop gonadal tumors and-when gonadectomized-adrenocortical carcinoma. The mechanisms leading to adrenal tumorigenesis have been proposed to involve the lack of a gonadal factor and/or a compensatory increase in gonadotropins. In order to achieve elevation of gonadotropins without the concomitant loss of a gonadal hormone, we crossed INH(-/-) mice with a transgenic mouse strain that has chronically elevated luteinizing hormone (LH) levels (LH-CTP). Compound INH(-/-)-LH-CTP mice die within 6 weeks of age from severe cancer cachexia induced by large, activin-secreting ovarian tumors. Unexpectedly, INH(-/-)-LH-CTP mice not only fail to develop adrenal tumors but have smaller adrenals, with a regressed x zone, indicating that elevated LH levels are not sufficient to induce adrenal tumor formation. However, following gonadectomy, INH(-/-)-LH-CTP mice develop large, sex steroid-producing adrenal tumors that arise from the x zone, indicating a growth-promoting effect of high levels of LH on the adrenal cortex in the absence of ovarian tumors. In addition, in vivo and in vitro data indicate that activin induces apoptosis specifically in the adrenal x zone. The restricted expression of activin receptor subunits and Smad2 in cells of the adrenal x zone, together with the elevated activin levels in INH(-/-)-LH-CTP mice, supports the conclusion that activin inhibits adrenal tumor growth by inducing x-zone regression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.