2013), while the vasoconstrictive RhoA/Rho-kinase signaling pathway is downregulated, further exacerbating priapism because of reduced vasoconstriction ( Bivalacqua et al. Oxidative stress is also increased in the SCD penis associated with upregulation of NADPH oxidase and eNOS uncoupling ( Kanika et al. Basally low levels of eNOS and NO downstream signaling in the penis in SCD are associated with decreased phosphodiesterase (PDE)5 regulatory function due to lack of the cGMP-dependent feedback control mechanism, resulting in unchecked cGMP accumulation in the penis upon neurostimulation and priapism ( Champion et al. Reduced nitric oxide (NO)/cGMP bioavailability in the penis related to decreased endothelial NO synthase (eNOS) activity is a principal molecular defect underlying priapism in SCD ( Champion et al. 2003, Burnett & Bivalacqua 2007, Bivalacqua et al. Recurrent ischemic priapism, a disorder of non-willful, excessive penile erection, associated with erectile tissue loss and erectile dysfunction, is a highly prevalent complication of SCD ( Montague et al. Sickle cell disease (SCD) is a consequence of a genetic mutation involving a single amino acid substitution in the beta subunit of hemoglobin, forming hemoglobin S ( Kato 2016). In conclusion, in the mouse model of human SCD, increasing testosterone to eugonadal levels reduced priapic activity and reversed impaired Akt/eNOS activity and PDE5 protein expression in the penis. Testosterone treatment did not affect P-nNOS (Ser-1412), eNOS, nNOS, or α smooth muscle actin protein expressions in the Sickle mouse penis. Testosterone treatment reduced (P<0.05) prolonged detumescence in Sickle mice, and normalized downregulated P-PDE5 (Ser-92), PDE5, P-eNOS (Ser-1177), and P-Akt (Ser-473) protein expressions in the Sickle mouse penis. Testosterone treatment reversed downregulated serum testosterone levels and increased (P<0.05) the weight of seminal vesicles in Sickle mice to levels comparable to that of WT mice, indicating restored testosterone levels in Sickle mice. Serum testosterone levels were measured by radioimmunoassay protein expressions of PDE5, α smooth muscle actin, eNOS and nNOS, and phosphorylation of PDE5 at Ser-92, eNOS at Ser-1177, neuronal (n)NOS at Ser-1412, and Akt at Ser-473, were measured by western blot in penile tissue. After 21 days, animals underwent erectile function assessment followed by collection of blood for serum testosterone measurements, penes for molecular analysis, and seminal vesicles as testosterone-responsive tissue. Adult male transgenic Berkeley sickle cell (Sickle) and wild type (WT) mice were implanted with testosterone pellets, which release 1.2 μg testosterone/day for 21 days, or vehicle. Given the critical role of androgens in erection physiology and NO synthase (NOS)/PDE5 expression, we hypothesized that testosterone replacement to eugonadal testosterone levels reduces priapism by reversing impaired endothelial (e)NOS activity and molecular abnormalities involving PDE5. Priapism is also associated with testosterone deficiency, but molecular mechanisms underlying testosterone effects in the penis in SCD are not known. Williams is also the host of the annual Sickle Cell Anemia Foundation nationally televised telethon.Sickle cell disease (SCD)-associated priapism is characterized by decreased nitric oxide (NO) signaling and downregulated phosphodiesterase (PDE)5 protein expression and activity in the penis. Hooker, The Waltons, Knots Landing, The White Shadow, What's Happening!!, Good Times, Quincy, M.E., Kung Fu, S.W.A.T., Gunsmoke, That Girl, and Sanford and Son. Law, Night Court, Magnum, P.I., Hill Street Blues, Gimme a Break, The Jeffersons, The Dukes of Hazzard, T.J. His other television credits include Moonlight, Moesha, Suddenly Susan, Minor Adjustments, L.A. He played the grandfather in the Bernie Mac film Guess Who. In the early to mid-1990s, he starred in many of comic Sinbad's productions, including The Sinbad Show and The Cherokee Kid. He was controversially fired from The Jimmy Stewart Show in 1971 at the insistence of its star, James Stewart. "Ted" Ross in the television series of the same name), and Clint Eastwood's The Rookie. Since then, he has appeared in movies such as Paul Schrader's Hardcore, Howard Zieff's Private Benjamin (he also portrayed the role of Sgt L.C. Williams started in the acting business in 1969. Halroy Candis Williams (born December 14, 1938) is an American actor, best known for his recurring role as Police Officer Smith ("Smitty") on Sanford and Son (1972–76) and as the patriarch Lester Jenkins, the husband of Marla Gibbs's character, on the NBCsitcom 227 (1985–90).īorn and raised in Columbus, Ohio, Williams worked as a postal worker and corrections officer before moving to Hollywood to pursue an acting career.
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