Dog Prostate Research Articles

Prostatic intraepithelial neoplasia in dogs with spontaneous prostate cancer

Prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer. The prevalence and immunophenotype of PIN in dogs with spontaneous prostate cancer has not been previously described. To investigate the association between PIN and prostate cancer, we evaluated the prostates of dogs with spontaneous prostate carcinoma. The prevalence of PIN was determined in formalin-fixed prostates from 29 dogs with spontaneous prostate cancer. Using immunoperoxidase techniques, we compared basal cell layer integrity (high molecular weight keratin 34 beta-E12), proliferative index (MIB-1), and microvessel density (Factor VIII-related antigen) in 14 prostates which contained benign epithelium, PIN, and carcinoma. PIN was present in 19 of 29 (66%) prostates from dogs with spontaneous prostate cancer. The basal cell layer was intact in benign epithelium, disrupted in 72% of acini with PIN, and absent in carcinoma. The mean proliferative index was 17%, 25%, and 40% for benign epithelium, PIN, and carcinoma, respectively, and these differences were significant. The mean microvessel density in foci of PIN and carcinoma (32 and 39 vessels per mm2, respectively) was greater than in benign epithelium (23 vessels per mm2). High-grade PIN is common in the prostates of dogs with spontaneous carcinoma. The basal cell layer is partially disrupted in PIN, whereas it is absent in prostate cancer. The proliferative index and microvessel density of PIN are intermediate between benign epithelium and cancer. These results are similar to those reported for human PIN and prostate cancer, and indicate that PIN is part of a morphologic continuum in the progression of prostate cancer. To our knowledge, this is the first description of high-grade PIN spontaneously occurring in animals. The canine prostate may serve as a useful model for examining factors that modulate PIN and prostate cancer progression. Prostate 30:92–97, 1997. © 1997 Wiley-Liss, Inc.

Prostatic intraepithelial neoplasia in dogs with spontaneous prostate cancer.

Prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer. The prevalence and immunophenotype of PIN in dogs with spontaneous prostate cancer has not been previously described. To investigate the association between PIN and prostate cancer, we evaluated the prostates of dogs with spontaneous prostate carcinoma. The prevalence of PIN was determined in formalin-fixed prostates from 29 dogs with spontaneous prostate cancer. Using immunoperoxidase techniques, we compared basal cell layer integrity (high molecular weight keratin 34 beta-E12), proliferative index (MIB-1), and microvessel density (Factor VIII-related antigen) in 14 prostates which contained benign epithelium, PIN, and carcinoma. PIN was present in 19 of 29 (66%) prostates from dogs with spontaneous prostate cancer. The basal cell layer was intact in benign epithelium, disrupted in 72% of acini with PIN, and absent in carcinoma. The mean proliferative index was 17%, 25%, and 40% for benign epithelium, PIN, and carcinoma, respectively, and these differences were significant. The mean microvessel density in foci of PIN and carcinoma (32 and 39 vessels per mm2, respectively) was greater than in benign epithelium (23 vessels per mm2). High-grade PIN is common in the prostates of dogs with spontaneous carcinoma. The basal cell layer is partially disrupted in PIN, whereas it is absent in prostate cancer. The proliferative index and microvessel density of PIN are intermediate between benign epithelium and cancer. These results are similar to those reported for human PIN and prostate cancer, and indicate that PIN is part of a morphologic continuum in the progression of prostate cancer. To our knowledge, this is the first description of high-grade PIN spontaneously occurring in animals. The canine prostate may serve as a useful model for examining factors that modulate PIN and prostate cancer progression.

Gossypol Induces Spermidine/SpermineN1-Acetyltransferase in Canine Prostate Epithelial Cells

Gossypol is an antisteroidogenic compound naturally found in cottonseed. Gossypol has been shown to inhibit steroidogenesis in the canine prostate and may inhibit canine prostate growth. Its mechanism of action, however, is largely unknown. Our laboratory has previously demonstrated that in vivo administration of gossypol to male dogs can reduce circulating levels of testosterone and estradiol. Gossypol also showed an ability to reduce prostate weights. To search for genes regulated by gossypol in the canine prostate, differential display RT-PCR was performed on total RNAs isolated from control and gossypol-treated male dogs. Gossypol was demonstrated to induce expression of spermidine/spermine-N1-acetyltransferase (SSAT), the major catabolic enzyme for polyamines. This induction was confirmed by Northern hybridization analysis of total RNA isolated from prostates of mature dogs treated with gossypol for 2 months. Gossypol was also shown to inhibit the progression of cells into the S phase mediated by spermidine. Our findings support the notion that gossypol can inhibit prostate cell proliferation and may be a potential therapeutic agent for use in controlling overgrowth of the prostate.

Measurement of tissue optical properties by time-resolved detection of laser-induced transient stress

We report on a technique utilizing time-resolved detection of laser-induced stress transients for the measurement of optical properties in turbid media specifically suitable for biological tissues. The method was tested initially in nonscattering absorbing media so that it could be compared with spectrophotometry. The basis of this method is provided by the conditions of temporal stress confinement in the irradiated volume where the pressure generated in tissues heated instantly by laser pulses is proportional to the absorbed laser energy density, and the exponential profile of the initial stress distribution in the irradiated volume corresponds to the z-axial distribution of the absorbed laser fluence. Planar thermoelastic waves can propagate in water-containing media with minimal distortion, and their axial profiles can be detected by an acoustic transducer with sufficient temporal resolution. The acoustic waves induced by 14-ns laser pulses in nonscattering media, turbid gels, and tissues were measured by a piezoelectric transducer with a 3-ns response time. Temporal profiles of stress transients yielded z-axial distributions of the absorbed laser energy in turbid and opaque media, provided that the speed of sound in these media was known. The absorption and effective scattering coefficients of beef liver, dog prostate, and human aortic atheroma at three wavelengths, 1064 nm (in near infrared), 532 nm (visible), and 355 nm (near UV), were deduced from laser-induced stress profiles with additional measurements of total diffuse reflectance.

Effects of a New Non-Steroidal 5α-Reductase Inhibitor, FK143, on the Prostate Gland in Beagle Dogs

FK143 (4-[3-[3-[bis(4-isobutylphenyl)methylamino]benzoyl]-1H-indol-1-yl]-butyric acid) is a new non-steroidal inhibitor of steroid 5α-reductase (5α-reductase). The effects of FK143 on prostate size and histopathology of mature male beagle dogs were investigated and compared with those of finasteride (a steroidal 5α-reductase inhibitor), and allylestrenol and Chlormadinone acetate (CMA) (androgen receptor antagonists). FK143 was orally administered to the dogs daily for 12 weeks. At doses of 10 and 32 mg/kg, FK143 significantly reduced prostate volume to about 60% of the initial value, and dogs treated with FK143 showed a dose-dependent glandular epithelial atrophy in the prostate. FK143 showed no abnormal changes in organ weights and histopathology of the adrenal, testis, pituitary and liver. The degree of prostate reduction in the dogs treated with FK143 (10 and 32 mg/kg) was almost the same as that by finasteride (1.0 mg/kg) and smaller than that by allylestrenol (10 mg/kg) or CMA (10 mg/kg). However, allylestrenol increased liver weights, and CMA increased liver and reduced adrenal weights. These results demonstrate that FK143 can decrease the volume of the dog prostate without any influence on other organs, and they suggest that FK143 is a good candidate for the treatment for benign prostatic hyperplasia.

Effects of a new non-steroidal 5 alpha-reductase inhibitor, FK143, on the prostate gland in beagle dogs.

FK143 (4-[3-[3-[bis(4-isobutylphenyl)methylamino]benzoyl]-1H-indol-1-yl] - butyric acid) is a new non-steroidal inhibitor of steroid 5 alpha-reductase (5 alpha-reductase). The effects of FK143 on prostate size and histopathology of mature male beagle dogs were investigated and compared with those of finasteride (a steroidal 5 alpha-reductase inhibitor), and allylestrenol and chlormadinone acetate (CMA) (androgen receptor antagonists). FK143 was orally administered to the dogs daily for 12 weeks. At doses of 10 and 32 mg/kg, FK143 significantly reduced prostate volume to about 60% of the initial value, and dogs treated with FK143 showed a dose-dependent glandular epithelial atrophy in the prostate. FK143 showed no abnormal changes in organ weights and histopathology of the adrenal, testis, pituitary and liver. The degree of prostate reduction in the dogs treated with FK143 (10 and 32 mg/kg) was almost the same as that by finasteride (1.0 mg/kg) and smaller than that by allylestrenol (10 mg/kg) or CMA (10 mg/kg). However, allylestrenol increased liver weights, and CMA increased liver and reduced adrenal weights. These results demonstrate that FK143 can decrease the volume of the dog prostate without any influence on other organs, and they suggest that FK143 is a good candidate for the treatment for benign prostatic hyperplasia.

Temperature rise recorded during lesion formation by high-intensity focused ultrasound

Temperature rise was observed as a function of time in liver and dog prostate tissue ex vivo during heating with high-intensity focused ultrasound. The temperature rise was measured using a needle thermocouple placed at the focus. The temperature vs. time behaviour closely followed the predictions of a model based on bulk and surface heating. When the tissue temperature was raised above 50°C, an increase in heating rate was seen. At higher temperatures, a point was reached at which a marked, irreversible change of tissue properties was observed, consistent with protein denaturation. The change was sometimes accompanied by a sudden further rise in temperature followed by an equally sudden fall. On dissection, regions of tissue damage (lesions) were seen, sometimes containing bubbles consistent with acoustic cavitation or vaporisation.

Estradiol activates p60 src, p53/56 lyn and renatured p50/55 protein tyrosine kinases in the dog prostate

Protein tyrosine kinases (PTKs) are key enzymes implicated in signal transduction pathways regulated by growth factors (GFs). We have previously shown by immunohistochemistry that the level of phosphotyrosine (pY) proteins is increased in prostatic basal epithelial cells following estrogen treatment in castrated dogs. In this study, we investigated if this treatment increases the level and distribution of prostatic PTK activity, and more specifically, if it alters the expression and/or activity of the Src family members p60 src and p53/56 lyn. Prostates from normal and hyperplastic dog prostates, as well as those from castrated dogs treated with androgens, were also examined. Only the glands obtained from estrogen-treated dogs had a significantly increased total and specific PTK activity, observed uniquely in the particulate extract, as compared to the other types of prostates studied. In addition, this increased activity was correlated upon gel filtration chromatography with the presence of an additional peak of activity with an apparent molecular weight of 130 kDa, which was absent in other prostate fractions presenting only 50 kDa peaks. Using antibodies, we demonstrate that active p60 src and p53/56 lyn kinases accounted for 81% of the activity in this 130 kDa peak. On the other hand, in situ renaturation also revealed the presence of still uncharacterized 50/55 kDa PTKs in the 130 kDa peak. Altogether, these findings raise the possibility that these PTKs contribute to the transmission of mitogenic signals originating directly or indirectly from estrogen stimulation of the basal cell layer of the prostate.

Induction of seminal vesicle morphogenesis from dog epididymal epithelium.

A number of carnivores, including the dog, do not have seminal vesicles (SVs). They have been induced experimentally by heterotypic recombination of adult dog epididymal epithelium with mesenchyme of neonatal rat SV and allowed to grow for 4 weeks under the renal capsule of male athymic nude mice. The induced SVs bore a striking similarity to rat SV both histologically and ultrastructurally. However, they secreted proteins which were different from those in the rat SV and reacted negatively to antibodies specific to rat SV secretory proteins and dog prostate secretory proteins. The results strongly suggested that the glands induced from dog epididymal epithelium were likely to be "dog" SVs.

Nitric oxide synthase-containing nerves and ganglia in the dog prostate: a comparison with other transmitters.

The distribution of nitric oxide synthase immunoreactive nerves in the dog prostate was compared to the total innervation (as estimated by protein gene product 9.5 immunoreactivity), and to that of adrenergic (tyrosine hydroxylase-immunoreactive), cholinergic (acetylcholinesterase-positive), and some peptidergic nerves immunoreactive towards vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and helospectin. Clusters of ganglia with cell bodies containing acetylcholinesterase, or one of these six immunoreactive components, were found in the dorsal capsule. Coarse nerve trunks expressing these immunoreactive components extended from the ganglia, and divided into varicose terminals in the capsule and intraglandular smooth muscle strands, and gave off further branches, which surrounded acini and accompanied ducts. The labelling for nitric oxide synthase generally coincided with that for vasoactive intestinal peptide within cell bodies and nerves of various types. Cell bodies, nerve trunks and varicose terminals showing labelling for pituitary adenylate cyclase-activating peptide and helospectin were generally also labelled for vasoactive intestinal peptide. The innervation pattern suggests that nitric oxide may act in concert with vasoactive intestinal peptide and related peptides in the control of prostatic smooth muscle activity and secretion.

Noninvasive ultrasonic subtotal ablation of the prostate in dogs

Abstract Objective To determine whether high-intensity focused ultrasound (HIFU) can be used for subtotal ablation of the prostate gland in dogs without causing damage to surrounding tissues. Design Experimental trial. Animals Adult hounds ≥5 years old and weighing between 20 and 30 kg. Procedure Prostatic ablation was performed in all dogs, using a transrectal HIFU probe. Acute effects of HIFU treatment were evaluated in 4 dogs. These dogs were euthanatized and necropsied 4 hours after the procedure. Chronic effects were evaluated in the other 3 dogs. Serial CBC, serum biochemical analyses, urinalyses, and transrectal ultrasonography were performed. Dogs were euthanatized and necropsied 3 months (1 dog) or 1 year (2 dogs) after HIFU treatment. Results Histologic examination of the prostate glands from the 4 dogs euthanatized 4 hours after treatment revealed that 80 to 90% of the gland had undergone hemorrhagic, liquefactive necrosis. Only slight discoloration of the prostatic capsule was detected, and there were not any gross or histologic lesions of the rectal mucosa or urinary bladder. All 3 dogs followed up after HIFU treatment developed cystic cavities within the prostate. Clinicopathologic testing did not indicate any long-term adverse effects. Conclusions and Clinical Relevance This method was effective in causing subtotal ablation of prostatic tissue in dogs. Further study of morbidity is required before the technique can be used clinically. (Am J Vet Res 1996; 57:1225-1227)

Effect of aromatase inhibitor, TZA-2209, on the prostate of androstenedione-treated castrated dogs: Changes in prostate volume and histopathological findings

To determine whether the inhibition of estrogen-related effect in the prostate would be of value in the management of benign prostate hyperplasia (BPH), we examined the effect of TZA-2209, a new steroidal aromatase inhibitor, on the prostate in three of six castrated beagles that received 75 mg/week androstenedione. The three other animals served as controls. Sequential measurements of prostate volume by transrectal ultrasonography showed that the volume in TZA-treated dogs was significantly decreased compared with that in the controls. Prostatic aromatase activity was suppressed by TZA administration. Histopathologically, the stromal component was increased and glands were atrophied by androstenedione treatment. TZA administration increased the volume of the glands. Immunohistochemical detection of estramustine-binding protein showed more positive staining of the protein in the glands that were increased in volume by TZA administration. We concluded that the aromatase inhibitor effectively antagonized the estrogen-related stromal changes, however, this action was accompanied by stimulation of the glandular component due to the accumulation of androgens, the substrate of the aromatase. In the light of these findings, we suggest the simultaneous treatment for the androgen-glandular component route in the prostate is necessary for the effective management of BPH.

Possible Mechanism of Induction of Benign Prostatic Hyperplasia by Estradiol and Dihydrotestosterone in Dogs

A mechanism of induction of canine benign prostatic hyperplasia (BPH) by androgen plus estrogen has been postulated to be based on androgen-stimulated growth of prostatic cells exposed to estrogen-induced toxicity. Estrogen is thought to be activated by redox cycling of catechol metabolites, a mechanism of generation of active radicals. Mongrel dogs, 4 animals/group, were sham-operated (controls) or were treated for 60 days with implants of 5α-dihydrotestosterone and/or estradiol-17β. The activities of drug and hormone metabolizing enzymes (aryl hydrocarbon hydroxylase, 7-ethoxycoumarinO-deethylase, and estradiol-17β-2- and -4-hydroxylase) in prostate were significantly elevated by chronic treatment with either estradiol-17β or 5α-dihydrotestosterone plus estradiol-17β, but not in kidney or liver which are not targets of hormone-induced hyperplasia. Activities of the detoxifying enzymes catalase and glutathione peroxidase I in prostate were increased by estradiol-17β treatment, whereas in kidney or liver they were not affected or changed to a lesser degree than observed in prostate. Free radical-induced damage (carbonyl content) of proteins was observed in prostate of dogs treated with either estradiol-17β or 5α-dihydrotestosterone plus estradiol-17β and in liver protein by treatment with either 5α-dihydrotestosterone or 5α-dihydrotestosterone plus estradiol-17β. It was concluded that the patterns of estradiol-17β- or 5α-dihydrotestosterone plus estradiol-17β-induced increases in activities of catechol estrogen synthase and of other drug metabolizing enzymes were consistent with the postulated free radical generation by redox cycling of catechol estrogen specifically in the prostate. The increases in activities of detoxifying enzymes may represent an (albeit insufficient) response to prostatic free radical damage. The covalent free radical damage to protein in prostate is consistent with a postulated induction of BPH via injury by estrogen metabolites followed by 5α-dihydrotestosterone-stimulated growth of altered prostatic cells.

Phosphotyrosine Antibodies Preferentially React with Basal Epithelial Cells in the Dog Prostate

Purpose Considering the hypothesis that androgen-independent but growth factor dependent epithelial cell division may be important in the development and progression of prostate cancer and that protein tyrosine kinases and phosphotyrosine protein phosphatases are key enzymes modulating the levels of specific phosphotyrosylated proteins implicated in several growth factor regulated signal transduction pathways, our aim was to study the cellular distribution of phosphotyrosine proteins in normal and hyperplastic dog prostates as well as in those of castrated dogs supplemented with either androgens or estrogens in order to modify the relative proportion of basal versus secretory epithelial cells. Materials and Methods Following the determination of optimal conditions to specifically detect phosphotyrosine proteins by a rabbit polyclonal antibody directed against phosphotyrosine, immunohistochemistry was performed on prostate tissue sections from these experimental animals. In addition to morphological criteria, an antibody to high molecular weight cytokeratins and antisera against arginine esterase were used to selectively identify basal and secretory cells. Since prostatic acid phosphatase may be involved in the local regulation of phosphotyrosine proteins, its distribution was also evaluated with a human prostatic acid phosphatase antiserum. Results In all prostatic tissues examined, basal epithelial cells were preferentially and specifically stained with antiphosphotyrosine. The staining intensity per basal cell was highest in the estrogen-supplemented dogs. In addition, basal cells were numerically increased and all were highly immunoreactive for high molecular weight cytokeratins. In prostates displaying a well-differentiated glandular epithelium, the number of positive basal cells and their staining intensity varied in the following order: normal less than hyperplastic less than androgen-supplemented dogs. At all times, the levels of phosphotyrosine proteins in prostatic acid phosphatase and arginine esterase positive cells (secretory) remained low. Fibroblasts and smooth muscle cells were unreactive to antiphosphotyrosine, even though estrogen supplementation increased the prostatic stromal volume. Conclusions The preferential localization of phosphotyrosine proteins in basal cells, their increased level per cell and the number of positive cells in the different experimental animals support the concept that basal cells represent the stem cells of the prostate. The sex steroid-mediated up-regulation of protein phosphorylation on tyrosine residues in these cells suggests that their proliferation is likely to involve growth factor regulated signal transduction pathways. In this respect, the lack of maturation of basal cells and the differentiation of secretory cells induced by androgen deprivation, combined with estrogen stimulation, favors the activation of these pathways and cell growth. On the other hand, the activation of glandular cell differentiation and the increase of stromal volume do not alter the threshold level of protein tyrosine kinase and phosphatase activities in secretory cells, fibroblasts and smooth muscle cells.

Age-dependent expression of the androgen receptor gene in the prostate and its implication in glandular differentiation and hyperplasia.

The senescence phenotype is the product of both cumulative physical damages during the life span and a species-specific genetic program. The genetic program of aging appears to have co-evolved with the sexual mode of reproduction. The same developmental processes that prepare the animal for maximum vitality and reproductive competence during young adulthood, if allowed to continue, can be detrimental during old age. Androgen receptor-mediated development and growth of the prostate gland is an example of such "antagonistic pleiotropy." The prostate gland is composed of two major groups of cells: the epithelial and stromal. Among the epithelial type, the columnar cells on the luminal surface produce the prostatic secretions, and the basal cells are presumed to serve as progenitors of the columnar cells. Within the stromal cell population, fibroblastic and smooth muscle cells are thought to produce growth factors that support the development and function of the epithelial cells. Both epithelial and stromal cells are dependent on androgens. In this study, we have examined age-dependent expression of the androgen receptor gene in the prostatic tissues of rats and dogs. Unlike the rat, in which the prostatic growth ceases after sexual maturation, the dog prostate continues to grow during aging. Similar to the dog, the antagonistic pleiotropy of the prostatic growth in the human causes the pathological condition of benign prostatic hyperplasia (BPH), the major health problem in old men. Quantitation of the androgen receptor (AR) mRNA in the total prostate extracts from young and old animals by the reverse transcriptase-polymerase chain reaction (RT-PCR) method showed about a 30% decline in AR mRNA in the 24-month-old rat prostate, as compared to the prostate of 3-month-old young adult animals. However, no significant difference in AR mRNA contents between 1-year-old and 10-year-old dog prostates was observed. In situ immunostaining for the androgen receptor protein revealed that in the case of rat, developmental maturation during the first month of life is associated with an increase in AR immunoreactivity in the luminal columnar epithelium, with a concomitant loss of immunoreactivity in the basal cells. Furthermore, with aging, there was a marked increase in the proportion of AR-negative basal cells in comparison to luminal columnar cells. Surprisingly, in both young adult (approximately 1-year-old) and old (approximately 10-year-old) dogs, most of the AR immunoreactivity was localized in the fibroblastic stromal cells rather than in the epithelial cells. Based on these observations and the existing literature, we propose that normally, in most mammalian species, an age-dependent decline in the conversion of basal to columnar epithelial cells after sexual maturation serves as a stop signal for the prostate growth. However, in certain species, such as the dog, robust AR expression in the stromal cells overrides this regulatory blockage and leads to prostatic hyperplasia in old age.

Phosphotyrosine Antibodies Preferentially React with Basal Epithelial Cells in the Dog Prostate

Phosphotyrosine Antibodies Preferentially React with Basal Epithelial Cells in the Dog Prostate

Effect of Orchiectomy on the Alpha Adrenergic Contractile Response of Dog Prostate

Purpose To investigate the effect of androgen deprivation on the alpha-adrenergic contractile response of the dog prostate using both in vitro and in vivo methods. Materials and Methods In vitro muscle bath study: One month after surgery, responses to KCl (120 mM.) and norepinephrine (10 sup -8 to 10 sup -3 M.) of prostatic tissue strips (of the same size) from castrated (n = 6) and sham-operated (n = 6) adult mongrel dogs were determined. In vivo study: Before and 1 month after surgery, the intraprostatic urethral pressure response to intravenous norepinephrine administration of 6 castrated and 5 sham-operated adult dogs was examined. Results (1) Before castration the serum level of testosterone was 1.24 plus/minus 0.2 ng./ml.; 1 month after castration, it had dropped to an undetectable level. (2) Histological examination of the prostates from castrated animals revealed profound atrophy of glandular tissue with a relatively increased stromal tissue component in each section. (3) In vitro study: The contractile responses to KC1 and norepinephrine of individual prostate strips (same size) from castrated animals were significantly higher than control. However, if the response to norepinephrine was normalized to the response to KCl, there was no significant difference in response to norepinephrine between the 2 groups. In addition, the ED 50 of the norepinephrine-stimulated contractile response was not changed by castration. (4) In vivo study: There was no significant change in intraprostatic urethral pressure response to intravenous norepinephrine administration after orchiectomy. Conclusions The results of this study show that the sensitivity of the alpha-adrenergic contractile response of the dog prostate is not affected by androgen deprivation, nor is alpha-adrenergic contractile activity of the dog prostate regulated by androgen.

Effect of Orchiectomy on the Alpha Adrenergic Contractile Response of Dog Prostate

Effect of Orchiectomy on the Alpha Adrenergic Contractile Response of Dog Prostate

5 alpha-Androstan-3 alpha,17 beta-diol is a hormone: stimulation of cAMP accumulation in human and dog prostate

5 alpha-Androstan-3 alpha,17 beta-diol is a hormone: stimulation of cAMP accumulation in human and dog prostate

5 alpha-Androstan-3 alpha,17 beta-diol is a hormone: stimulation of cAMP accumulation in human and dog prostate.

5 alpha-Androstan-3 alpha, 17 beta-diol (3 alpha-diol) is a well known metabolite of dihydrostestosterone (DHT) and the concentration of its glucuronide in serum is looked upon as a marker of DHT activity in skin and prostate. The data in this communication show that 3 alpha-diol is a potent agonist of the human and canine prostatic SHBG-[SHBG receptor]. It causes a robust rise in intracellular cAMP within minutes; the 1/2 max. response occurs at a concentration equal to its concentration in male plasma. Estradiol is the only other agonist in this system. All other steroids that bind to SHBG are antagonists.