General Medical Information

Leydig Cell Hypoplasia

Joe Leigh Simpson

In complete absence of Leydig cells, 46,XY cases have female external genitalia, no uterus, and bilateral testes devoid of Leydig cells. Epididymides and vasa deferentia are present, and serum LH is elevated. Affected siblings have been reported and parental consanguinity observed. Thus, autosomal recessive inheritance has long been accepted.

The molecular basis involves mutation in the LHR gene, located on chromosome 2. Kremer etreported two siblings of consanguineous parents; homozygosity for a missense mutation (Ala(593) ®Pro) existed. In another case, Salameh detected a deletion in exon 11. Leydig cells presumably fail to develop because LH cannot exert its effect during embryogenesis. This is reminiscent of ovarian failure due to FSHR mutation.

In contrast to the inactivating LHR mutations, activating mutations cause precocious puberty in males. In females, LHR activating receptor mutations do not seem to exert the same effect.