title: Artificial masculinization in tilapia involves androgen receptor activation.
abstract: Estrogens have a pivotal role in natural female sexual differentiation of tilapia while lack of steroids results in testicular development. Despite the fact that androgens do not participate in natural sex differentiation, synthetic androgens, mainly 17-α-methyltestosterone (MT) are effective in the production of all-male fish in aquaculture. The sex inversion potency of synthetic androgens may arise from their androgenic activity or else as inhibitors of aromatase activity. The current study is an attempt to differentiate between the two alleged activities in order to evaluate their contribution to the sex inversion process and aid the search for novel sex inversion agents. In the present study, MT inhibited aromatase activity, when applied in vitro as did the non-aromatizable androgen dihydrotestosterone (DHT). In comparison, exposure to fadrozole, a specific aromatase inhibitor, was considerably more effective. Androgenic activity of MT was evaluated by exposure of Sciaenochromis fryeri fry to the substance and testing for the appearance of blue color. Flutamide, an androgen antagonist, administered concomitantly with MT, reduced the appearance of the blue color and the sex inversion potency of MT in a dose-dependent manner. In tilapia, administration of MT, fadrozole or DHT resulted in efficient sex inversion while flutamide reduced the sex inversion potency of all three compounds. In the case of MT and DHT the decrease in sex inversion efficiency caused by flutamide is most likely due to the direct blocking of the androgen binding to its cognate receptor. The negative effect of flutamide on the efficiency of the fadrozole treatment may indicate that the masculinizing activity of fadrozole may be attributed to excess, un-aromatized, androgens accumulated in the differentiating gonad. The present study shows that when androgen receptors are blocked, there is a reduction in the efficiency of sex inversion treatments. Our results suggest that in contrast to natural sex differentiation, during sex inversion treatments, androgens, either endogenous or exogenous, participate in inducing testicular differentiation.
authors.affiliation: Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
authors.forename: Matan
authors.initials: M
authors.lastname: Golan
authors.affiliation: Department of Animal Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel. Electronic address: berta.sivan@mail.huji.ac.il.
authors.forename: Berta
authors.initials: B
authors.lastname: Levavi-Sivan
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001141:Aromatase / Q000737:chemistry / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000494:pharmacology; D017316:Fadrozole / Q000494:pharmacology; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D006066:Gonads / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D008297:Male; D008777:Methyltestosterone / Q000494:pharmacology; D011944:Receptors, Androgen / Q000378:metabolism*; D012733:Sex Differentiation / Q000187:drug effects; D017210:Tilapia / Q000502:physiology*
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D005485:Flutamide; D001141:Aromatase; D017316:Fadrozole; D008777:Methyltestosterone
keywords: 17-α-Methyltestosterone; Aromatase; Fadrozole; Sex inversion; Tilapia