Roles for Nkx3.1 in prostate development and cancer.
In aging men, the prostate gland becomes hyperproliferative and displays a propensity toward carcinoma. Although this hyperproliferative process has been proposed to represent an inappropriate reactivation of an embryonic differentiation program, the regulatory genes responsible for normal prostate development and function are largely undefined. Here we show that the murine Nkx3.1 homeobox gene is the earliest known marker of prostate epithelium during embryogenesis and is subsequently expressed at all stages of prostate differentiation in vivo as well as in tissue recombinants. A null mutation for Nkx3.1 obtained by targeted gene disruption results in defects in prostate ductal morphogenesis and secretory protein production. Notably, Nkx3.1 mutant mice display prostatic epithelial hyperplasia and dysplasia that increases in severity with age. This epithelial hyperplasia and dysplasia also occurs in heterozygous mice, indicating haploinsufficiency for this phenotype. Because human NKX3.1 is known to map to a prostate cancer hot spot, we propose that NKX3.1 is a prostate-specific tumor suppressor gene and that loss of a single allele may predispose to prostate carcinogenesis. The Nkx3.1 mutant mice provide a unique animal model for examining the relationship between normal prostate differentiation and early stages of prostate carcinogenesis. (+info)
Metabolism of oestrone and oestradiol-17beta to conjugated steroids by the accessory sex glands of the male pig.
Oestrogens are secreted in large amounts by boar testes and are known to have a synergistic effect with testosterone on the production of large volumes of seminal plasma. Thus, oestrogens play a role in regulating the large accessory sex glands in the boar. Since testosterone metabolites (e.g. 5alpha-dihydrotestosterone) account for much of its action in target tissues we have looked at the metabolism of oestrogens in the accessory sex glands of the male pig. Tissues from seminal vesicles and bulbourethral glands of 6-week-old castrate and intact males, and 12-week-old castrate animals, were incubated with (3)H-labelled oestrone and oestradiol-17beta. Aliquots of spent culture medium and of methanolic tissue extracts were taken to measure radioactivity, prior to separation of unconjugated and conjugated steroids on Waters C(18) Sep-Pak cartridges. About one-third of the radioactivity appeared as conjugates in the media from both glands with each oestrogen. Subsequently, sulphoconjugated steroids and glucuronidates were recovered in series from C(18) cartridges after solvolysis and enzyme hydrolysis respectively. Furthermore, about one-third of the conjugated fraction in each case remained unhydrolysed after these treatments. In conclusion, it is clear that a study of the actions of oestrogens on these glands must consider the dynamics of metabolism of the oestrogens presented to them by the testes and would include conjugation of steroids by the glands themselves. (+info)
Social effects and boar taint: significance for production of slaughter boars (Sus scrofa).
A study was conducted to elucidate the effects of social factors on the concentrations of boar taint substances, androstenone and skatole, in boars. The factors included dominance (social rank) and the effects of strongly tainted animals on other members of the group. Four successive replicates of 100 pigs (50 boars + 50 gilts) with an average live weight of 24 kg were randomly allocated to 10 pens of 10. Data for this study were collected during the period of 67 to 114 kg of live weight and included the repetitive recording of agonistic behavior during competitive feeding; blood sampling for determination of plasma androstenone, skatole and testosterone in boars; feces sampling for determination of skatole content; and collection of bulbourethral glands in boars, and uteri plus ovaries in gilts at slaughter, for the assessment of sexual maturity. Results show an influence of social rank on plasma concentrations of androstenone (P = .0001) and testosterone (P = .0001), the weight of the bulbourethral glands (P = .0001), and plasma skatole (P = .02). Pens were classified according to the pig with the highest concentration of androstenone in the pen into high, medium, and low maximum pens. In pens with high maximum concentrations of androstenone, the second-highest androstenone concentration (P = .0001), and the average concentration (P = .0003) in the pen were higher than those in pens with medium or low maximum concentrations of androstenone. Mean aggression level was also higher (P = .02), but pens with high maximum aggression level did not have higher mean androstenone concentration. Rank effect on androstenone was more important than aggression effect. Neither maximum androstenone concentration nor maximum aggression level in a pen was related to the pen mean stage of sexual maturity in either sex. No influences of rank, aggression, or aggression received were found on the feces skatole level, and no pheromonal communicative function was demonstrated for skatole. High androstenone concentrations did not have a suppressive effect on androstenone concentrations in other males of the group; on the contrary, the levels were increased. This may be due to a stimulating effect of androstenone and, possibly, mating activity. Consequently, in the production of boars for slaughter, strongly tainted animals should be avoided or removed and mating activity minimized. This could be facilitated by, for instance, slaughtering before sexual maturity or separate rearing of the sexes. (+info)
Expression of the lipocalin-type prostaglandin D synthase gene in the reproductive tracts of Holstein bulls.
The aim of this study was to localize expression of the prostaglandin D synthase gene in the reproductive tracts of Holstein bulls using northern blotting and in situ hybridization. For northern blotting, a digoxigenin-labelled prostaglandin D synthase cDNA probe was used to probe blots containing RNA isolated from the testes, epididymides, vas deferens, ampullae, seminal vesicles, prostate and bulbourethral glands of bulls. The digoxigenin-labelled cDNA for the bovine homologue of prostaglandin D synthase hybridized to a single band (approximately 0.9 kb) to RNA samples from the caput, corpus and cauda epididymides, as well as RNA samples from the vas deferens and the ampulla. The probe also detected a single band in testis samples, although the transcript size was slightly larger (approximately 1.0 kb) than the transcript found in the other tissues. The highest expression of prostaglandin D synthase was observed in the testes and caput epididymides. Prostaglandin D synthase transcripts were not found in the seminal vesicles or the prostate or bulbourethral glands using northern blotting. For in situ hybridization, antisense and sense riboprobes were synthesized and used to hybridize to cryosections obtained from the reproductive tissues of bulls. In situ hybridization of bull testes showed that prostaglandin D synthase transcripts were present within the germ cells in the adluminal compartment of the seminiferous tubules containing round and elongated spermatids, indicating that expression varied with stage of development of the seminiferous tubules. Prostaglandin D synthase expression was observed in the epithelial cells of the epididymides with greatest expression occurring in the caput epididymidis. Some expression was also observed in the epithelial cells of the vas deferens and a few cells of some lobules in the prostate and bulbourethral glands. Expression of the prostaglandin D synthase gene was not detected in ampullae or seminal vesicles by in situ hybridization. (+info)
Vaccination of boars with a GnRH vaccine (Improvac) eliminates boar taint and increases growth performance.
Peri- and postpubertal boars accumulate substances (e.g., androstenone and skatole) in their fatty tissue that are responsible for boar taint in pork. The objective of this study was to assess the efficacy of a GnRH vaccine, Improvac, in eliminating boar taint. Three hundred male (200 intact boars, 100 barrows) crossbred (Large White x Landrace) pigs were used in a 2 x 3 factorially arranged experiment. The respective factors were sex group (barrows, boars treated with placebo, or boars treated with Improvac) and slaughter age (23 or 26 wk). Vaccines were administered 8 and 4 wk before slaughter. All Improvac-treated pigs exhibited anti-GnRH titers. Testes and bulbo-urethral gland weights in treated pigs were reduced by approximately 50% (P < 0.001) and serum testosterone levels were below 2 ng/mL in the majority of treated boars (94 and 92% across both age groups at 2 and 4 wk, respectively). Boar taint, as assessed by the concentration of androstenone and skatole in s.c. fat, was suppressed to low or undetectable levels in 100% of Improvac-treated boars. No Improvac-treated pigs had significant concentrations of either androstenone (> 1.0 microg/g) or skatole (> 0.20 microg/g). In contrast, 49.5% of placebo-treated controls had significant androstenone and 10.8% had significant skatole levels, resulting in 10% of the control boars with high concentrations of both compounds. The mean concentrations of taint compounds in the Improvac-treated pigs were not significantly different from those in barrows. Improvac-treated boars grew more rapidly (P = 0.051 and < 0.001 for pigs slaughtered at 23 and 26 wk of age, respectively) than control boars over the 4 wk after the secondary vaccination, possibly because of reduced sexual and aggressive activities. Compared with barrows, Improvac-treated boars were leaner and had superior feed conversion efficiency. The vaccine was well tolerated by the pigs, and no observable site reactions could be detected at the time of slaughter. Vaccination of boars with Improvac allows production of heavy boars with improved meat quality through prevention and control of boar taint. (+info)
Sites of production of fructose and citric acid in the accessory sex glands of the male musk shrew, Suncus murinus.
The main source of citric acid in the accessory sex glands of the musk shrew (Suncus murinus) was the prostate and fructose was abundantly produced by the ampullary glands. (+info)
Transforming growth factor-beta 2 heterozygous mutant mice exhibit Cowper's gland hyperplasia and cystic dilations of the gland ducts (Cowper's syringoceles).
Analyses of mutant mice with a deletion for the transforming growth factor beta 2 (Tgfbeta2) gene revealed cysts in the perineal/scrotal region of male mice. We present evidence from in situ, light and electron microscopy that the cysts observed in Tgfbeta2+/- heterozygous mice males derive from Cowper's gland tissue. The Cowper's glands of Tgfbeta2+/- heterozygous mutant mice display all steps of glandular hyperplasia and cystic dilation. TGF-beta isoforms and TGF-beta receptor (TbetaR-II) were localized immunocytochemically in sections of Cowper's glands. TGF-beta2 and TGF-beta3 were located predominantly in myoepithelial cells of the Cowper's gland whereas the TbetaRII was found in the plasma membrane of the acinar cells. TUNEL-assays revealed that apoptotic cell death is significantly reduced in Cowper's glands of TgfbetaB2+/- heterozygous mutant mice. The fact that Tgfbeta2+/- heterozygous mutant mice exhibit hyperplasia of Cowper's gland epithelium and Cowper's gland cysts suggests a disturbance of epithelial-stromal interaction most likely due to reduced TGF-beta2 level, accompanied by a significant decrease in apoptosis. (+info)
Structure of the pelvic and penile urethra--relationship with the ducts of the sex accessory glands of the Mongolian gerbil (Meriones unguiculatus).
The urethra is the main place of entry for sexually transmitted pathogens. However, there is little literature on the morphology of the urogenital system, principally the urethra and ducts of the sex accessory glands. The Mongolian gerbil is an insectivorous, herbivorous and monogamous rodent with nocturnal habits; it has been used successfully as a laboratory animal since the 1960s. Therefore, the objective of the present paper was to describe the structure and ultrastructure of the urethra and its relations to the ducts of the accessory sex glands of the Mongolian gerbil (Meriones unguiculatus), contributing to the understanding of the reproductive biology of the rodent and aiming to provide data for future experimental studies. Conventional techniques of light and scanning electron microscopy were utilized. The urethra and ducts of the accessory sex glands are similar to those of the albino rat and the mouse. However, there is variation in drainage type among accessory sex glands for the inner urethra. The ducts of the seminal vesicle, the ductus deferens, drain their contents independently into the ampullary duct that opens in the urethra. The ducts of the prostate, coagulating and bulbourethral glands drain their contents independently into the urethra. (+info)