title: c-erbAalpha and c-erbaAbeta in the Leydig cell repopulation by ethane-1,2-dimethanesulphonate model of mature rats.
abstract: BACKGROUND
  The regulatory effect of thyroid hormones on the proliferation and maturation of the Leydig cells (LC) in testis is still poorly understood. To date, it remains obscure whether the thyroid hormones have direct effect on the LC, as far as in rat testis the thyroid hormones receptors are localized predominantly in the Sertoli cells. A single intraperitoneal dose of cytotoxin ethane-1,2-dimethanesulphonate (EDS) injected into mature rats caused a rapid, selective elimination of the adult LC associated with temporary impairment of fertility. Regeneration of the LC population by EDS model is a result of the differentiation of LC progenitors as well as of the proliferation of the newly formed LC whereas the process is similar with the development of adult LC in the prepubertal testis.
  
  
  OBJECTIVE
  The present study aimed to establish the immunohistochemical expression of high affinity triiodothyronine nuclear receptors c-erbAalpha and c-erbAbeta in the regenerating LC after treatment with EDS of mature rats.
  
  
  METHODS
  Mature male Wistar rats were divided into two groups: (1) a group of rats receiving a single intraperitoneal (i.p.) injection of EDS (75 mg/kg body weight) and (2) a group of control animals. The animals were killed 24 hours, 7, 14, 21 and 35 days after treatment. Testicular fragments were prepared for routine histological and immunohistochemical examinations.
  
  
  RESULTS
  The immunohistochemical analysis revealed similar changes in the immunoreactivity for both c-erbAalpha and c-erbAbeta after EDS administration. On day 1 after EDS treatment, the intensity of the immune reactions for c-erbAalpha and c-erbAbeta in the LCs decreased simultaneously with their number. Seven days after EDS administration there was neither LCs nor c-erbAalpha nor c-erbAbeta-immunoreactivity. The first positive stained LCs were found 14 days after EDS when LCs progenitors were detected. The most prominent c-erbAalpha- and c-erbAbeta-immunostaining in the regenerating LCs was evident 21 days after EDS; this coincided with the increased number of LCs progenitors and their transformation into adult LCs population. Thirty-five days after EDS c-erbAalpha and c-erbAbeta-positive LCs were abundant their number and localization in the testicular interstitium being very similar to that in the control rats.
  
  
  CONCLUSIONS
  The observed change in the intensity of the immune reactions for c-erbAalpha and c-erbAbeta in LC repopulation after EDS treatment corresponds to the process of differentiation of progenitors into mature LC. The results obtained support the idea about the regulatory role of thyroid hormones in the differentiation of LC in prepubertal rat testis.
authors.affiliation: Department of Anatomy, Histology and Embryology, Medical University, Plovdiv, Bulgaria.
authors.forename: Yvetta A
authors.initials: YA
authors.lastname: Koeva
authors.forename: Mariana V
authors.initials: MV
authors.lastname: Bakalska
authors.forename: Ninan N
authors.initials: NN
authors.lastname: Atanassova
authors.forename: Michail S
authors.initials: MS
authors.lastname: Davidoff
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D007150:Immunohistochemistry; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008698:Mesylates / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D037021:Thyroid Hormone Receptors alpha / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism*
chemical_list: D008698:Mesylates; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; C002994:ethylene dimethanesulfonate