Endocrine Abstracts (2008) 16 OC5.8

The effect of estrogens plus cyproterone acetate or orchiectomy on serum insulin like factor 3 (INSL3) levels in transsexual men

Luigi Maione1, Alessandro Palmieri2, Giuseppe Bellastella1, Daniela Visconti1, Maria Chiara Quinto1, Annamaria De Bellis1, Vincenzo Mirone2, Antonio Bellastella1 & Antonio Agostino Sinisi1

1Endocrinology, Second University of Napoli, Napoli, Italy; 2Urology, Federico II University, Napoli, Italy.

The regulation of insulin-like factor 3 (INSL3) secretion from Leydig cells is still incompletely clarified. In this study we measured INSL3 serum levels in transsexual men under estrogen (E) and antiandrogen therapy or after orchiectomy. The effects of gonadotropins on testicular secretion in vitro was also evaluated.

Methods: Blood samples were obtained from 14 transsexual men under long-term E (n=5) or E plus cyproterone acetate (E+CPA, n=9) therapy. Samples were also drawn in 5 TS before and after 1, 3, 7 and 30 days from orchiectomy for gender change. Normal control plasma level was evaluated on ten adult men (NC). Short-term testicular tissue cultures were set-up and INSL3 secretion evaluated in medium obtained basally or after 72-h treatment with hCG, rFSH or both. INSL3 was measured in serum or medium using a commercial kit (Phoenix, Germany).

Results: Serum INSL3 resulted significantly reduced in TS assuming E+CPA (175±17 vs both TS E treated 346±57 and NC.711±76 pg/ml, P<0.0001). In all TS treated with E+CPA LH values were undetectable. INSL3 levels decreased immediately after orchiectomy (baseline 267±80, 1st day 89±5.8) remaining lower on 30th day. hCG induced a sharp INSL3 increase in vitro (+107%), whereas rFSH did not affect NSL3 secretion.

Conclusion: Reduced serum LH and INSL3 levels in E+CPA treated TS and hCG/LH stimulation of INSL3 release from testicular tissue in vitro confirm that LH plays a major role in regulating testicular secretion. Although detectable serum INSL3 levels in orchiectomized TS suggest an extra gonadal surge, marked decline immediately after surgery indicates that testes are the main site of INSL3 production in men.