title: Testosterone implants modify the steroid hormone balance and the gonadal physiology of gilthead seabream (Sparus aurata L.) males.
abstract: Androgens can induce complete spermatogenesis in immature or prepubertal teleost fish; however, many aspects of the role of androgens in adult teleost spermatogenesis remain elusive. We used the in situ forming microparticle (ISM) system containing 1mg of testosterone (T)/kg body weight (T-ISM) in a homogenous population of gilthead seabream at testicular involution stage to study in vivo the effects of T on the sex steroid hormone balance and on the physiology of the gilthead seabream gonad. The levels of T, 11-ketotestosterone (11KT) and 17β-estradiol (E2) in plasma, gonad and liver were determined in T-ISM implanted specimens after 7, 14, 21 and 28 days. The effect of T-ISM was evaluated on (i) de novo synthesis and metabolism of T in the gonad and liver by measuring the gene expression levels of the main steroidogenic proteins involved, (ii) the progress of spermatogenesis, (iii) the presence of different leukocyte cell types in the gonad, and (iv) the mRNA expression of some genes involved in the leukocyte migratory influx into the gonad and of some immune-relevant molecules. T-ISM implants promote an increase of T up to supra-physiological levels which induce a depletion of E2 levels and maintain the 11KT levels at physiological concentrations. The gene expression profile of some steroidogenic enzymes in gonad and liver ruled out the transformation of T into estrogenic compounds following T-ISM implantation. Moreover, androgens may also be involved in the leukocyte migratory influx, which occurred even when cytokine, chemokine and cell adhesion molecule gene expressions were down-regulated. Moreover, T-ISM implants block germ cell proliferation, although increased dmrt1 gene expression may prevent the complete depletion of germ cells in the gonad. Furthermore, T down-regulated the expression of several tlr genes, which may result in the inhibition of the immune response in the gonad through the impaired ability to recognize and respond to pathogens.
authors.affiliation: Centro Oceanográfico de Murcia, Instituto Español de Oceanografía (IEO), Carretera de la Azohía s/n, Puerto de Mazarrón, 30860 Murcia, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Sánchez-Hernández
authors.forename: Elena
authors.initials: E
authors.lastname: Chaves-Pozo
authors.forename: Isabel
authors.initials: I
authors.lastname: Cabas
authors.forename: Victoriano
authors.initials: V
authors.lastname: Mulero
authors.forename: Alfonsa
authors.initials: A
authors.lastname: García-Ayala
authors.forename: Alicia
authors.initials: A
authors.lastname: García-Alcázar
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000097:blood* / Q000378:metabolism*; D006066:Gonads / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D021541:Sea Bream / Q000097:blood* / Q000378:metabolism*; D013739:Testosterone / Q000031:analogs & derivatives / Q000097:blood* / Q000494:pharmacology
chemical_list: D012739:Gonadal Steroid Hormones; D013739:Testosterone; D004958:Estradiol; C003600:11-ketotestosterone
keywords: 11-ketotestosterone; 11KT; 11β- hydroxysteroid dehydrogenase gene; 11β-hydroxytestosterone; 17α-ethinyl estradiol; 17β-estradiol; 3β-hydroxysteroid dehydrogenase gene; 5α reductase gene; 5α-androstane-3β17β-diol; AGs; AR; CC chemokine 4 gene; DHT; E(2); EDCs; EE(2); G7; GSI; Gilthead seabream; HSI; ISM; IgM; Leukocytes; MB; MG; MH; OHT; P; PCNA; RCs; Steroidogenic enzymes; T; TUNEL; Testis; Testosterone; acidophilic granulocytes; androgen receptor; aromatase gene; body mass; body weight; bw; ccl4; cholesterol side chain cleavage cytochrome P450 gene; cyp11a1; cyp11b1; cyp19a1a; days post-implantation; dihydrotestosterone; dmrt1; double sex-and mab3-related transcription factor 1 gene; dpi; endocrine disrupting chemicals; gonad mass; gonadosomatic index; hepatic mass; hepatosomatic index; hsd11b; hsd3b; il1b; immunoglobulin M; in situ detection of DNA fragmentation; in situ forming microparticle implant; interleukin 1β gene; leukocyte adhesion molecule E-selectin gene; mAb; mAb specific to gilthead seabream AGs; monoclonal antibody; proliferating cell nuclear antigen; reproductive cycles; rsp18; sele; significance level; srd5a; star; steroid 11-beta-hydroxylase gene; steroidogenic acute regulatory protein gene; testosterone; tgfb1; the ribosomal protein S18 gene; tlr; tnfa; toll-like receptor gene; transforming growth factor β1 gene; tumour necrosis factor α gene; βdiol