Abstract
Mechanism(s) involved in regulating Intratesticular Testosterone levels (iT) have assumed importance in recent years, from the point of view of hormonal contraception. Contraceptives using Testosterone (T) in combination with Progestins (P), for more effective suppression of pituitary gonadotropins thereby iT, are not 100% effective in suppressing spermatogenesis in human males, likely due to pesrsistence of Intratesticular Dihydrotestosterone (iD) in poor-responders. Several lacunae pertaining to the mechanism of action of principal male hormone T during spermatogenesis remain to be resolved. Notably, the mechanism through which T brings about the stage-specific differentiation of germ cells lacking Androgen Receptors (AR). Testosterone is a highly anabolic steroid with a rapid tissue clearance rate. T is intratesticular substrate for synthesis of Dihydrotestosterone (DHT) and Estradiol (E2) involved in spermtaogenesis. Therefore, it is important to delineate the mechanism(s) for retention of iT, in order to understand regulation of its bioavailability in testis. In depth studies, pertaining to the role of androgen-binding protein(s) in sequestration, retention and bioavailability of T/DHT are required to understand male fertility regulation. The appropriate approach to overcome this lacuna would be development of mice lacking functional testicular Androgen-Binding Protein (ABPKO), but not deficient T/DHT, Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH), in order to understand its physiological functions. Insights gained about androgen retention mechanism(s) from the ABPKO murine model will be of immense help in improving the efficacy of male hormonal contraceptives and infertility management.
Highlights
Testosterone (T) is a lipophilic steroidal molecule synthesized in the interstitial cells of Leydig in the testis
These pathophysiological effects are characteristic of E2 exposure, seen in rats treated with specific ESR1 and ESR2 receptor agonists [15, 33, 44, 45]
In order to overcome the potential developmental problems of viability and cryptorchidism, a conditional knockout of Sertoli cell shbg gene would be an appropriate approach to study the role of Androgen-Binding Protein (ABP) in intratesticular testosterone (iT) retention and spermatogenesis
Summary
Testosterone (T) is a lipophilic steroidal molecule synthesized in the interstitial cells of Leydig in the testis. These studies detected reductions in transcripts of transition proteins, protamine, Arpc1b, Evl, Picalm, Bcl, Bclw, cyclin A1 and B1spermatidal genes in adult male rats with specific agonists of ESRI/2 (PPT and DPN) These studies confirmed the role of iE via testicular estrogen receptors ESR1 and ESR2 [16, 33]. Histological assessment of ABP h transgenic mouse testis revealed apoptosis of germ cells arrested at meiotic stage These pathophysiological effects are characteristic of E2 exposure, seen in rats treated with specific ESR1 and ESR2 receptor agonists [15, 33, 44, 45]. In order to overcome the potential developmental problems of viability and cryptorchidism, a conditional knockout of Sertoli cell shbg gene would be an appropriate approach to study the role of ABP in iT retention and spermatogenesis
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