title: Molecular adaptations of testosterone-producing Leydig cells during systemic in vivo blockade of the androgen receptor.
abstract: This study systematically evaluates the effects of androgen receptor (AR) blockade on molecular events in Leydig cells. Results showed that intramuscular administration of testosterone-enanthate, at clinically relevant dose, decreased testosterone in interstitial fluid and Leydig cells from adult rats. AR-blocker (Androcur) prevented this effect and testosterone-reduced Leydig cells steroidogenic capacity/activity. Testosterone-reduced expression of some steroidogenic enzymes/proteins (Tspo,StAR,Hsd3b1/2) and transcription factors (Nur77,Gata4,Dax1) was completely abrogated, while decreased expression of Star,Cyp11a1,Cyp17a1,Hsd17b4,Creb1a was partially prevented. In the same cells, increased expression of Hsd3b5/HSD3B and Ar/AR was abolished. Androcur-treatment abolished testosterone-reduced cAMP, coupled with a changed expressional milieu of cAMP signaling elements. Results from in vitro experiments suggest that some of these effects are testosterone-AR dependent, while others could be due to disturbed LH and/or other signals. Presented data provide new molecular insight into Leydig cells function and are important in terms of human reproductive health and the wide-spread use of Androcur as well as use/abuse of testosterone-enanthate.
authors.affiliation: Reproductive Endocrinology and Signaling Group, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Maja M
authors.initials: MM
authors.lastname: Bjelic
authors.affiliation: Reproductive Endocrinology and Signaling Group, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Natasa J
authors.initials: NJ
authors.lastname: Stojkov
authors.affiliation: Reproductive Endocrinology and Signaling Group, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Aleksandar Z
authors.initials: AZ
authors.lastname: Baburski
authors.affiliation: Reproductive Endocrinology and Signaling Group, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Srdjan J
authors.initials: SJ
authors.lastname: Sokanovic
authors.affiliation: Reproductive Endocrinology and Signaling Group, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Aleksandar I
authors.initials: AI
authors.lastname: Mihajlovic
authors.affiliation: Reproductive Endocrinology and Signaling Group, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Marija M
authors.initials: MM
authors.lastname: Janjic
authors.affiliation: Reproductive Endocrinology and Signaling Group, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Tatjana S
authors.initials: TS
authors.lastname: Kostic
authors.affiliation: Reproductive Endocrinology and Signaling Group, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia. Electronic address: silvana.andric@dbe.uns.ac.rs.
authors.forename: Silvana A
authors.initials: SA
authors.lastname: Andric
mesh_terms: D000222:Adaptation, Physiological; D059002:Androgen Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D017373:Cyproterone Acetate / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007986:Luteinizing Hormone / Q000235:genetics* / Q000378:metabolism; D008297:Male; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013251:Steroid Isomerases / Q000235:genetics* / Q000378:metabolism; D013739:Testosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D059002:Androgen Receptor Antagonists; D011944:Receptors, Androgen; D014157:Transcription Factors; D013739:Testosterone; D017373:Cyproterone Acetate; C004648:testosterone enanthate; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D013251:Steroid Isomerases
keywords: Androcur; Leydig cells; Steroidogenic machinery; Testosterone; cAMP signaling