The identification of a second oestrogen receptor (beta) has prompted a re-evaluation of the potential sites of action of oestrogens. The aim of the present study was to characterize immunoexpression of ER beta expression in the testis to complement earlier data which had demonstrated that expression of ER alpha is confined to testicular interstitial Leydig cells. In all testes studied, including those from both fetal (day 20.5 p.c.) and adult rats, ER beta was found to be expressed in multiple cell types. Sertoli cell nuclei were immunopositive at all ages. In adult testes expression in Sertoli cells was not stage dependent and was unaffected by ablation of Leydig cells. In fetal testes ER beta was also expressed in peritubular cells, fetal Leydig cells and gonocytes. In the pubertal and adult testis ER beta was detected in the nuclei of spermatogonia and most pachytene spermatocytes. Weak immunopositive staining was present in the cytoplasm of spermatocytes undergoing the second meiotic division. In conclusion the widespread expression of ER beta in the testis is consistent with a role for oestrogens in modulating spermatogenesis, and hence fertility, in the male.

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Rapid and complete withdrawal of intratesticular testosterone was achieved via the destruction of all Leydig cells with the specific Leydig cell cytotoxin ethane dimethanesulphonate (EDS). Restoration of testosterone levels was accomplished by administration of a single dose (25 mg) of testosterone esters (T) known to reverse the antispermatogenic effects of androgen withdrawal. Quantitation of the degenerating germ cells in cross sections of seminiferous tubules (ST) at stages IV-V, VII, IX, and X-XI of the spermatogenic cycle was used as a sensitive biological index of the effects of testosterone withdrawal and restoration upon the function of the Sertoli cells. Compared to control testicular tissues, the mean numbers of pyknotic germ cells per ST cross section at stages VII, IX and X-XI increased significantly (P < 0.01-0.001) between 4 to 8 days post-EDS treatment, but only in stage VII tubules was this trend reversed significantly (P < 0.005) within 2 days by T supplementation. In EDS-treated rats, stages VII, VIII, IX, and X-XI also exhibited significant (P < 0.05-0.001) increases (compared to controls) in the volumetric proportions by which intraepithelial vacuoles appeared within the seminiferous tubules. Again, in EDS+T supplemented rats, the appearance of vacuoles was significantly (P < 0.001) suppressed in stage VII and VIII. In contrast to tubules at stages VII-XI, those at stages IV-V were completely unaffected by testosterone withdrawal or replacement. The results show that at selected time intervals after EDS treatment, testosterone supplementation is capable of preventing/reversing these morphological changes within 2 days in stage VII tubules. It is suggested that the induction and subsequent prevention of seminiferous epithelial damage will serve as an important in vivo and in vitro approach for studies on the androgen-mediated changes in Sertoli cell biology during phases of impairment and recovery of their function. Manipulation of adult Sertoli cell function as provided by our model should permit identification of androgen-regulated gene products together with an understanding of their role(s) in normal and abnormal spermatogenesis.

Androgen receptor (AR) distribution and developmental regulation in the rat ovary were examined by semiquantitative immunohistochemistry. Ovarian AR mRNA levels were also determined by Northern analysis of total RNA and compared with the levels of cytochrome P450aromatase (P450arom), an established marker of preovulatory follicular maturity. Hypophysectomized immature female rats were treated with recombinant human (rh)-FSH and/or rh-LH, or human menopausal gonadotrophin (HMG). AR was predominantly located in granulosa cells. There was no indication of specific AR immunoreactivity in thecal cells, but scattered stromal cells did stain positively. In control and LH-treated ovaries, only small preantral/early antral follicles were present. Granulosa cells in these follicles showed intense AR immunostaining. Treatment with FSH, FSH and LH or HMG stimulated varying degrees of preovulatory follicular development. In these follicles, the intensity of AR immunostaining progressively declined as follicular development progressed. In intact immature rats treated with FSH, the abundance of ovarian AR mRNA was significantly decreased to 35% of the control value while combined treatment of FSH and LH resulted in further down-regulation of AR mRNA expression to 17% of the control value. A decrease in the abundance of AR mRNA was accompanied by a simultaneous increase in the abundance of P450arom mRNA. Similar results were obtained in hypophysectomized immature rats treated with FSH and LH, suggesting an inverse relationship between AR mRNA expression and granulosa cell maturity. These results suggest that (1) the AR is most abundant in the granulosa cells of rat ovaries and (2) the expression of AR and its mRNA are developmentally regulated, being down-regulated during FSH-stimulated preovulatory follicular development.

Acinetobacter spp. are increasingly reported as important causes of human infection. Many isolates exhibit multi-drug resistance, raising concerns over our ability to treat serious infections with these organisms. The impact of infection on clinical outcome as well as the importance of multi-drug resistance is poorly defined. A descriptive retrospective observational study was undertaken of all episodes of Acinetobacter bacteremia occurring in a UK tertiary care centre from 1998-2006. Demographics of infected patients, characteristics and antimicrobial susceptibility of infecting strains were recorded and the impact of antimicrobial therapy on all causes of 30-day mortality assessed. Three hundred ninety-nine episodes of Acinetobacter bacteremia were identified, with A. baumannii being the most frequently isolated species. Most episodes occurred in critical care and were associated with multidrug resistance, with carbapenem resistance rising from 0% in 1998 to 55% in 2006. Although bacteremia due to carbapenem-resistant Acinetobacter and a requirement for critical care were associated with a higher mortality, mortality was not reduced by the administration of appropriate empirical antimicrobial therapy. A prospective study is required to identify both the most effective intervention and those most likely to benefit from treatment.