title: Alteration of the hypothalamic-pituitary-gonadal axis in estrogen- and androgen-treated adult male leopard frog, Rana pipiens.
abstract: BACKGROUND
  Gonadal steroids, in particular 5 alpha-dihydrotestosterone (DHT) and 17 beta-estradiol (E2), have been shown to feed back on the hypothalamic-pituitary-gonadal (HPG) axis of the ranid frog. However, questions still remain on how DHT and E2 impact two of the less-studied components of the ranid HPG axis, the hypothalamus and the gonad, and if the feedback effects are consistently negative. Thus, the goal of the study was to examine the effects of DHT and E2 upon the HPG axis of the gonadally-intact, sexually mature male leopard frogs, Rana pipiens.
  
  
  METHODS
  R. pipiens were implanted with silastic capsules containing either cholesterol (Ch, a control), DHT, or E2 for 10 or 30 days. At each time point, steroid-induced changes in hypothalamic GnRH and pituitary LH concentrations, circulating luteinizing hormone (LH), and testicular histology were examined.
  
  
  RESULTS
  Frogs implanted with DHT or E2 for 10 days did not show significant alterations in the HPG axis. In contrast, frogs implanted with hormones for 30 days had significantly lower circulating LH (for both DHT and E2), decreased pituitary LH concentration (for E2 only), and disrupted spermatogenesis (for both DHT and E2). The disruption of spermatogenesis was qualitatively similar between DHT and E2, although the effects of E2 were consistently more potent. In both DHT and E2-treated animals, a marked loss of all pre-meiotic germ cells was observed, although the loss of secondary spermatogonia appeared to be the primary cause of disrupted spermatogenesis. Unexpectedly, the presence of post-meiotic germ cells was either unaffected or enhanced by DHT or E2 treatment.
  
  
  CONCLUSIONS
  Overall, these results showed that both DHT and E2 inhibited circulating LH and disrupted spermatogenesis progressively in a time-dependent manner, with the longer duration of treatment producing the more pronounced effects. Further, the feedback effects exerted by both steroid hormones upon the HPG axis were largely negative, although the possibility exists for a stimulatory effect upon the post-meiotic germ cells.
authors.affiliation: Department of Integrative Physiology and the Center for Neuroscience, University of Colorado, Boulder, CO 80309-0354, USA. pei-san.tsai@colorado.edu
authors.forename: Pei-San
authors.initials: PS
authors.lastname: Tsai
authors.forename: Ann E
authors.initials: AE
authors.lastname: Kessler
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Jones
authors.forename: Kathleen B
authors.initials: KB
authors.lastname: Wahr
mesh_terms: D000818:Animals; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D025461:Feedback, Physiological; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007031:Hypothalamus / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D011894:Rana pipiens; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000166:cytology / Q000187:drug effects*
chemical_list: D013196:Dihydrotestosterone; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone