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Genetics Home Reference: your guide to understanding genetic conditions
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Leydig cell hypoplasia

Reviewed April 2010

What is Leydig cell hypoplasia?

Leydig cell hypoplasia is a condition that affects male sexual development. It is characterized by underdevelopment (hypoplasia) of Leydig cells in the testes. Leydig cells secrete male sex hormones (androgens) that are important for normal male sexual development before birth and during puberty.

In Leydig cell hypoplasia, affected individuals with a typical male chromosomal pattern (46,XY) may have a range of genital abnormalities. Affected males may have a small penis (micropenis), the opening of the urethra on the underside of the penis (hypospadias), or a scrotum divided into two lobes (bifid scrotum). Because of these abnormalities, the external genitalia may not look clearly male or clearly female (ambiguous genitalia).

In more severe cases of Leydig cell hypoplasia, people with a typical male chromosomal pattern (46,XY) have female external genitalia. They have small testes that are undescended, which means they are abnormally located in the pelvis, abdomen, or groin. People with this form of the disorder do not develop secondary sex characteristics, such as increased body hair, at puberty. Some researchers refer to this form of Leydig cell hypoplasia as type 1 and designate less severe cases as type 2.

How common is Leydig cell hypoplasia?

Leydig cell hypoplasia is a rare disorder; its prevalence is unknown.

What genes are related to Leydig cell hypoplasia?

Mutations in the LHCGR gene cause Leydig cell hypoplasia. The LHCGR gene provides instructions for making a protein called the luteinizing hormone/chorionic gonadotropin receptor. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and their receptors trigger signals that affect cell development and function.

The protein produced from the LHCGR gene acts as a receptor for two ligands: luteinizing hormone and a similar hormone called chorionic gonadotropin. The receptor allows the body to respond appropriately to these hormones. In males, chorionic gonadotropin stimulates the development of cells in the testes called Leydig cells, and luteinizing hormone triggers these cells to produce androgens. Androgens, including testosterone, are the hormones that control male sexual development and reproduction. In females, luteinizing hormone triggers the release of egg cells from the ovary (ovulation). Chorionic gonadotropin is produced during pregnancy and helps maintain conditions necessary for the pregnancy to continue.

The LHCGR gene mutations that cause Leydig cell hypoplasia disrupt luteinizing hormone/chorionic gonadotropin receptor function, impeding the body's ability to react to these hormones. In males, the mutations result in poorly developed or absent Leydig cells and impaired production of testosterone. A lack of testosterone interferes with the development of male reproductive organs before birth and the changes that appear at puberty. Mutations that prevent the production of any functional receptor protein cause the more severe features of Leydig cell hypoplasia, and mutations that allow some receptor protein function cause milder signs and symptoms.

Related Gene(s)

Changes in this gene are associated with Leydig cell hypoplasia.

  • LHCGR

How do people inherit Leydig cell hypoplasia?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Only people who have mutations in both copies of the LHCGR gene and are genetically male (with one X and one Y chromosome in each cell) have the characteristic signs of Leydig cell hypoplasia. Although people who are genetically female (with two X chromosomes in each cell) may inherit mutations in both copies of the LHCGR gene, they do not have Leydig cell hypoplasia because they do not have Leydig cells. They have normal female genitalia and normal breast and pubic hair development, but they may begin menstruation later than usual (after age 16) and have irregular menstrual periods. LHCGR gene mutations in females also prevent ovulation, leading to inability to have children (infertility).

Where can I find information about diagnosis or management of Leydig cell hypoplasia?

These resources address the diagnosis or management of Leydig cell hypoplasia and may include treatment providers.

  • Genetic Testing Registry: Leydig cell agenesis (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0266432)
  • MedlinePlus Encyclopedia: Ambiguous Genitalia (http://www.nlm.nih.gov/medlineplus/ency/article/003269.htm)
  • MedlinePlus Encyclopedia: Hypospadias (http://www.nlm.nih.gov/medlineplus/ency/article/001286.htm)
  • MedlinePlus Encyclopedia: Intersex (http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm)

You might also find information on the diagnosis or management of Leydig cell hypoplasia in Educational resources (http://ghr.nlm.nih.gov/condition/leydig-cell-hypoplasia/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/leydig-cell-hypoplasia/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Leydig cell hypoplasia?

You may find the following resources about Leydig cell hypoplasia helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Leydig cell hypoplasia?

  • LCH
  • Leydig cell agenesis
  • LH resistance due to LH receptor deactivation
  • male hypergonadotropic hypogonadism due to LHCGR defect
  • 46,XY disorder of sex development due to LH defects

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Leydig cell hypoplasia?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Leydig cell hypoplasia?

agenesis ; androgens ; autosomal ; autosomal recessive ; bifid ; cell ; chromosome ; egg ; gene ; genitalia ; groin ; hormone ; hypogonadism ; hypoplasia ; hypospadias ; infertility ; inherit ; inherited ; menstruation ; micropenis ; ovary ; pelvis ; prevalence ; protein ; puberty ; receptor ; recessive ; reproduction ; scrotum ; testes ; testosterone

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Kossack N, Simoni M, Richter-Unruh A, Themmen AP, Gromoll J. Mutations in a novel, cryptic exon of the luteinizing hormone/chorionic gonadotropin receptor gene cause male pseudohermaphroditism. PLoS Med. 2008 Apr 22;5(4):e88. doi: 10.1371/journal.pmed.0050088. (http://www.ncbi.nlm.nih.gov/pubmed/18433292?dopt=Abstract)
  • Qiao J, Han B, Liu BL, Chen X, Ru Y, Cheng KX, Chen FG, Zhao SX, Liang J, Lu YL, Tang JF, Wu YX, Wu WL, Chen JL, Chen MD, Song HD. A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism. Hum Mutat. 2009 Sep;30(9):E855-65. doi: 10.1002/humu.21072. (http://www.ncbi.nlm.nih.gov/pubmed/19551906?dopt=Abstract)
  • Themmen AP, Verhoef-Post M. LH receptor defects. Semin Reprod Med. 2002 Aug;20(3):199-204. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12428200?dopt=Abstract)
  • Wu SM, Chan WY. Male pseudohermaphroditism due to inactivating luteinizing hormone receptor mutations. Arch Med Res. 1999 Nov-Dec;30(6):495-500. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10714363?dopt=Abstract)
  • Wu SM, Leschek EW, Rennert OM, Chan WY. Luteinizing hormone receptor mutations in disorders of sexual development and cancer. Front Biosci. 2000 Mar 1;5:D343-52. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10704433?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2010
Published: August 25, 2014