Cited by 49Sexual Differentiation and DisordersAdrenal Hormones and DisordersGenetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Human 3β-hydroxysteroid dehydrogenase deficiency seems to affect fertility but may not harbor a tumor risk: lesson from an experiment of nature

Burckhardt, Marie-Anne, Udhane, Sameer S, Marti, Nesa, Schnyder, Isabelle, Tapia, Coya, Nielsen, John E, Mullis, Primus E, Rajpert-De Meyts, Ewa +1 more·2015·European Journal of Endocrinology

Abstract

CONTEXT: 3β-hydroxysteroid dehydrogenase deficiency (3βHSD) is a rare disorder of sexual development and steroidogenesis. There are two isozymes of 3βHSD, HSD3B1 and HSD3B2. Human mutations are known for the HSD3B2 gene which is expressed in the gonads and the adrenals. Little is known about testis histology, fertility and malignancy risk. OBJECTIVE: To describe the molecular genetics, the steroid biochemistry, the (immuno-)histochemistry and the clinical implications of a loss-of-function HSD3B2 mutation. METHODS: Biochemical, genetic and immunohistochemical investigations on human biomaterials. RESULTS: A 46,XY boy presented at birth with severe undervirilization of the external genitalia. Steroid profiling showed low steroid production for mineralocorticoids, glucocorticoids and sex steroids with typical precursor metabolites for HSD3B2 deficiency. The genetic analysis of the HSD3B2 gene revealed a homozygous c.687del27 deletion. At pubertal age, he showed some virilization of the external genitalia and some sex steroid metabolites appeared likely through conversion of precursors secreted by the testis and converted by unaffected HSD3B1 in peripheral tissues. However, he also developed enlarged breasts through production of estrogens in the periphery. Testis histology in late puberty revealed primarily a Sertoli-cell-only pattern and only few tubules with arrested spermatogenesis, presence of few Leydig cells in stroma, but no neoplastic changes. CONCLUSIONS: The testis with HSD3B2 deficiency due to the c.687del27 deletion does not express the defective protein. This patient is unlikely to be fertile and his risk for gonadal malignancy is low. Further studies are needed to obtain firm knowledge on malignancy risk for gonads harboring defects of androgen biosynthesis.

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Crossref · 10.1530/eje-15-0599

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  • HSD3B2 deficiency causes DSD in both sexes: genetic females are mildly virilized because some fetal adrenal DHEA is converted to testosterone by HSD3B1; genetic males synthesize some androgens by peripheral conversion of DHEA, but these are insufficient for complete male genital development.

    “HSD3B2 deficiency causes DSD in both sexes: genetic females are mildly virilized because some fetal adrenal DHEA is converted to testosterone by HSD3B1; genetic males synthesize some androgens by peripheral conversion of DHEA, but these are insufficient for complete male genital development (59).”

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Authors
Burckhardt, M.-A., Udhane, S. S., Marti, N., Schnyder, I., Tapia, C., Nielsen, J. E., Mullis, P. E., Rajpert-De Meyts, E., & Flück, C. E.
Affiliations
University of Bern (CH)
Corresponding author
Flück, Christa E
Venue
European Journal of Endocrinology
Published
2015-11
Volume
173
Issue
5
Pages
K1-K12
ISSN
  • 0804-4643 (ISSN-L)
  • 1479-683X
OpenAlex
W2107795317
Cited by
49
References
45
Citations by year
2026: 3 · 2025: 5 · 2024: 3 · 2023: 7 · 2022: 6 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 1 · 2015: 1
FWCI
1.74
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • BORIS (University Library Bern) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Keywords
3β-hydroxysteroid dehydrogenase deficiency, HSD3B2, HSD3B1, 46,XY disorders of sex development, testicular histology, Leydig cells, fertility, gonadal malignancy risk, androgen production, breast augmentation, steroid profiling
MeSH terms
Adrenal Hyperplasia, Congenital, Humans, Infant, Newborn, Infertility, Male, Male, Mutation, Puberty, Testis

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