Evaluation of endocrine testing of Leydig cell function using extractive and recombinant human chorionic gonadotropin and different doses of recombinant human LH in normal men

Abstract

Background: The functional testing of endocrine testis uses extractive human chorionic gonadotropin (ehCG). Recombinant human hCG (rhCG), avoiding any contamination, should replace ehCG. Moreover, a functional evaluation with recombinant human LH (rhLH) would be closer to physiology than a pharmacological testing with hCG. Methods: The study was conducted in normal men. We first evaluated the dose-effect of ehCG on plasma testosterone and estradiol levels, before and after injection of either hCG or vehicle. Secondly, the responses to the optimal dose of ehCG were compared with those of rhCG. Thirdly, we investigated the dose-effect of rhLH, on steroid hormone secretion. LH, testosterone, and estradiol plasma levels were measured after the injection of either rhLH or placebo. Results: ehCG induced dose-dependent increases in plasma estradiol and testosterone levels. They respectively peaked at 24 and 72 h after the injection. The most potent dose of ehCG (5000 IU) induced results similar to those observed with 250 mg (6500 IU) rhCG. By comparison with placebo, rhLH induced a significant and dose-dependent increase in plasma testosterone levels 4 h after the injection. Peak response of testosterone to rhLH and rhCG was significantly correlated. rhLH did not induce significant change in plasma estradiol level. Conclusions: In normal men, a single i.v. injection of 150 IU rhLH induces a 25% rise in plasma testosterone levels by comparison with placebo. At the moment, the dynamic evaluation using hCG remains the gold standard test to explore the Leydig cell function. The use of 250 mg rhCG avoiding any contamination should be recommended.

Gonadal response after a single-dose stimulation test with recombinant human chorionic gonadotropin (rhCG) in patients with isolated prepubertal cryptorchidism

“…The interval of 7 days after rhCG for hormonal assessment was chosen after a pilot study of five individuals in which hormonal data was measured at 3, 5, 7 and 10 days after rhCG; in this subjects testosterone peak response was obtained after 7 days. A previous study in adult healthy men found similar testosterone peak after 250 mcg rhCG and uhCG 5000 UI [6]. In vitro fertilization studies analysing oocyte maturation did not find significant differences in pharmacokinetics between both compounds [5, 7].…”

LH and hCG Action on the Same Receptor Results in Quantitatively and Qualitatively Different Intracellular Signalling

“…Previous in vitro [36] and in vivo [37]–[39] studies did not pick up differences between the effects of hCG and hLH, probably because they were based on gonadotropins not quantified in exact molar terms but in “units” calibrated against a third preparation, e.g. the standard International Standard WHO 80/522 [18], or using in vivo bioassay (rat seminal vesicle weight gain assay).…”

Human Chorionic Gonadotropin Test: Old Uncertainties, New Perspectives, and Value in 46,XY Disorders of Sex Development

“…The authors found similar peak responses with such doses; the testosterone peak responses were reached 72 h after injections, and the mean testosterone increase over the baseline was 2.27-and 2.25-fold with uhCG and rhCG, respectively. The use of recombinant LH (rLH) determined a peak response after 4 h from intravenous injection, but the increment was about 25% from baseline values, confirming that hCG is able to attain a higher and longer stimulation of LH/CG receptor than LH itself [De Martino et al, 2003;Cailleux-Bounacer et al, 2008].…”