A study by Hyne and Boettcher ( 31 ) reported the existence of specific, low-affinity binding sites for 17β-E 2 on human spermatozoa for which other steroids could compete. A subsequent autoradiographic study observed that the binding of[ 3 H]17β-E 2 to spermatozoa can be reduced by coincubation with other steroids, such as progestagens, which can strongly compete for the 17β-E 2 receptor ( 32 ). The presence of high-affinity (K D × 10 −10 m ) binding sites for 17β-E 2 on human sperm has been further confirmed: after fractionation of 17β-E 2 -bound spermatozoa, they are detectable mainly in the membrane fraction (75–85%), whereas the nuclear fractions shows only about 10% of the total bound radioactivity, and no radioactivity is detected in the cytosolic fraction ( 33 ). Other autoradiographic data confirm that the plasma membrane is the site of receptors with specificity for 17β-E 2 , which are mostly concentrated in the central part of the sperm tail ( 34 ). In competition experiments, the binding sites for [ 3 H]17β-E 2 appear to be specific, the labeled steroid being displaced by cold 17β-E 2 . Specific binding sites for [ 3 H]17β-E 2 are not detectable in the sperm cytosol and in sperm nuclei isolated after homogenization, detergent treatment, and centrifugation ( 35 ).
The appropriate regulation of androgen activity is necessary for a range of developmental and physiological processes, particularly male sexual development and maturation. However, excessive production of adrenal androgens can cause premature puberty in young boys and their hypersecretion in females, may produce a masculine pattern of body hair and cessation of menstruation (). Their mis-regulation is also implicated in the formation and progression of prostatic adenocarcinoma (). Therefore, the removal of testicular androgens by castration has long been recognized to result in tumor regression, and surgical or pharmacological androgen ablation remain the predominant form of treatment for advanced prostate cancer. Androgen ablation therapy is often combined with treatment with nonsteroidal antiandrogens, such as hydroxyflutamide, to block residual adrenal androgen action. Androgen Replacement Therapy has been in use for over 60 years to treat, with proven efficacy and safety, on patients with male hypogonadal disorders and/or failure of sexual development. Apart from that, the last decade has witnessed a wider therapeutic role of androgens for nonclassical indications. These include male contraception; aplastic anemia; and sarcopenic, osteopenic, and depressive states frequently associated with an expanding variety of chronic systemic conditions (characterized by reduced circulating testosterone) such as AIDS, rheumatoid arthritis, chronic renal failure, chronic obstructive airways disease, and physiological aging ().