title: Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1-eNOS axis.
abstract: Aging and physiological androgen decay leads to structural changes in corpus cavernosum (CC) that associate with erectile function impairment. There is evidence that such changes relate to nitric oxide (NO) bioavailability, an endothelial compound produced by the action of endothelial NO synthase (eNOS), and is regulated by sirtuin-1 (Sirt1), a NAD(+)-dependent protein deacetylase. Taking into account the reduced NO synthesis observed in aging and erectile dysfunction, we aimed to characterize human CC of androgen-deprived, young, and aged individuals postulating that androgen deprivation induces modifications similar to those observed in aging. Human penile fragments were collected from young individuals submitted to male-to-female sex reassignment procedure, who undergone an androgen deprivation chemical regimen, from young organ donors and from aged patients submitted to penile deviation surgery. They were processed for histomorphometric analysis of smooth muscle (SM) and connective tissues (CT), and dual-immunofluorescence of alpha-actin/vWf or Sirt1, and endothelin-1/eNOS. Estrogen receptors were analyzed by immunohistochemistry and semiquantification of Sirt1, eNOS, and phospho-Akt was assayed by Western blotting. Androgen withdrawal, similarly to aging, leads to a noteworthy reduction of SM-to-CT ratio in CC. However, in contrast to young and aged, a significant increase in penile Sirt1 expression accompanied by an increase in total eNOS expression was observed in androgen-depleted individuals. No changes were evidenced in phospho-Akt system and estrogen receptors were undetectable. These findings indicate that Sirt1 regulates the expression of eNOS in human CC employing mechanisms influenced by androgen depletion.
authors: Department of Experimental Biology, Faculty of Medicine of Universidade do Porto, Alameda Prof. Hernâni Monteiro, Porto, Portugal. inestomada@gmail.com
authors: Inês
authors: I
authors: Tomada
authors: Nuno
authors: N
authors: Tomada
authors: Henrique
authors: H
authors: Almeida
authors: Delminda
authors: D
authors: Neves
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology*; D000728:Androgens / Q000378:metabolism*; D015153:Blotting, Western; D007172:Erectile Dysfunction / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis*; D010410:Penile Erection / Q000502:physiology*; D010413:Penis / Q000378:metabolism*; D056564:Sirtuin 1 / Q000096:biosynthesis*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000728:Androgens; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C447939:SIRT1 protein, human; D056564:Sirtuin 1