Premium
The ABC transporter Mrp4 (Abcc4) plays a crucial role in normal testosterone production
Author(s) -
Morgan Jessica A,
Adachi Masashi,
Boyd Kelli,
Neale Geoff,
Wang Yao,
Cheepala Satish,
Scheffer George L,
Schuetz John D
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1015.9
Subject(s) - testosterone (patch) , spermatogenesis , endocrinology , medicine , leydig cell , biology , transporter , luteinizing hormone , gene , hormone , genetics
The primary site of testosterone biosynthesis in males occurs in the Leydig cells of the testes. Accordingly, circulating levels of testosterone exhibit a developmental pattern that correlate to the amount of testosterone produced. We show that, in the testes of both mouse and man, Mrp4 is almost exclusively expressed in the Leydig cells. Prior to puberty, despite normal Leydig cell numbers, Mrp4−/− mice have dramatically reduced serum testosterone concentrations when compared to their Mrp4+/+ counterparts. Consistent with this finding, Mrp4−/− mice exhibited both impaired spermatogenesis and prostate development. Nonetheless, adult Mrp4−/− animals are fertile with no obvious reproductive defects. After puberty, circulating testosterone concentrations of the Mrp4−/− mouse rise to levels comparable to those of the Mrp4+/+ mouse. In the Mrp4−/− mouse we have identified a developmental mechanism that accounts for the low levels of testosterone prior to puberty and the unexpected subsequent rise post‐puberty. These findings indicate that Mrp4 function has a crucial role in the appropriate developmental production of systemic testosterone. Funding provided by the NIH and ALSAC.