Venous drainage and functional control of the canine prostate gland.

The venous drainage of the canine prostate gland has been studied in nine dogs after post-mortem intravenous injection of a coloured suspension of latex. A submucosal cavernous plexus of the prostatic urethra continuous with that of the penis, and a previously unnamed vessel that drains this plexus into the prostatico-vesical vein are described. The eferential vein was found to open variably, but always into the prostatic venous system. The data support the concept that a very small retrograde blood flow would take androgen-rich blood from the deferential vein into the prostate gland.

Demonstration of a specific cytosol receptor in the normal and hyperplastic canine prostate for 5alpha-androstane-3alpha, 17alpha-diol.

A specific receptor protein has been demonstrated for 5alpha-androstane-3alpha, 17alpha-diol in cytoplasmic extracts of normal and hyperplastic canine prostates. The receptor molecule, with a sedimentation coefficient of 4-5S, has been identified by the use of sucrose gradient centrifugation of tissue fractions which had been labelled in vitro with tritiated 5alpha-androstane-3alpha, 17alpha-diol. The receptor showed a relatively high affinity for this compound whereas binding could not be demonstrated with other labelled C19 steroids. In addition binding of tritiated 5alpha-androstane-3alpha, 17alpha-diol was not affected by the presence of 50-fold excesses of other C19 steroids.

Studies on the uptake and binding of 5alpha-androstane-3alpha, 17alpha-diol by canine prostatic nuclei.

Nuclei have been isolated from canine prostatic tissue previously incubated with tritiated testosterone or tritiated 5alpha-androstane-3alpha, 17alpha-diol. The protein-bound radioactivity has, in both cases, been shown to be associated with 5alpha-androstane-3alpha, 17alpha-diol. The formation and translocation of this steroid to the nucleus supports previous evidence that it has an active part to play in prostatic function in the dog. The formation from testosterone of another titriated steroid, possibly 5alpha-dihydrotestosterone, was also demonstrated although this product did not enter the nucleus and was apparently bound to the nuclear membrane.

Hormonal effects on canine prostatic explants in organ culture.

Explants of canine prostate were cultured in a defined medium for periods of up to 5 days with and without added steroids. Testosterone and 5 alpha-dihydrotestosterone failed to maintain their histological integrity and induced a greatly increased formation of stromal elements. Epitestosterone and 5 alpha-dihydroepitestosterone were partially successful in maintaining epithelial height although secretory activity was not preserved. The only steroid that sustained epithelial height and secretory activity whilst keeping stromal growth at a minimum was 5 alpha-androstane-3 alpha, 17 alpha-diol. The three other epimeric androstanediols were ineffective.

Demonstration of a cytoplasmic receptor protein for oestrogen in the canine prostate gland.

A receptor protein that selectively binds oestrogens has been demonstrated in the cytosol of the canine prostate gland. The steroid--receptor complex was found to have a sedimentation coefficient of 4--5 S with respect to bovine serum albumin after sucrose density-gradient centrifugation. The high affinity and low capacity of the protein for oestrogens was indicated by displacement studies, which gave a value of 3.8 +/- 1.53 (S.D.) X 10(-10) mol/l for the dissociation constant. A metastasizing prostatic tumour was also shown to possess this receptor, with binding properties similar to those exhibited by the receptor in normal prostatic cytosol. The implications of these findings are discussed with regard to normal prostatic function in the dog and the virtually inevitable advent of prostatic hyperplasia with age in this species.

Measurement of cortisol, cortisone, 11-deoxycortisol and corticosterone in foetal sheep plasma during the perinatal period.

A method is described for the resolution and individual quantitation of cortisol, cortisone, 11-deoxycortisol and corticosterone in foetal sheep plasma. The steroids were extracted by solvent partition and separated by LH-20 Sephadex column chromatography. Radioimmunoassay was used for the measurement of 11-deoxycortisol and cortisone and competitive protein-binding for corticosterone and cortisol. The relative levels of these steroids in the plasma of chronically catheterized sheep foetuses from 12 days before birth to term and then in the newborn lamb until 2 days of age are recorded. Cortisol gradually increased from a basal concentration of between 0 - 5 and 3 - 0 mug/100 ml plasma between days 12 and 5 pre partum, and then rose rapidly to 10 mug/100 ml plasma during the last 5 days of pregnancy to reach a maximum during or just after birth. Two days post partum the levels had fallen to approximately 3 mug/100 ml plasma. The mean value for 11-deoxycortisol between days 8 and 3 pre partum was 0 - 4 mug/100 ml plasma and increased in the final days before delivery to 1 - 0 mug/100 ml. Corticosterone initially showed slightly higher levels (approximately 1 - 5 mug/100 ml) in the earlier period of investigation but then fell during the immediate pre-partum period to 0 - 8 mug/100 ml. Cortisone was not detected at any stage of the investigations. The relationship between levels of cortisol and 11-deoxycortisol in foetal plasma and myometrial contractility is shown. An increase in uterine activity was seen to occur at the time that cortisol levels were at their maximum. The 11-deoxycortisol values throughout this particular study remained low. The results are discussed in relation to recorded levels in the adult and to previous studies in vitro with regard to changing steroid biosynthetic enzyme activity.

An examination of blood steroid and gonadotropin concentrations in relation to fertility status and testicular function in men.

Plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), testosterone (T), and 17 beta-estradiol (E2) have been measured in men complaining of infertility in comparison with men of proven fertility. Subgrouping of patients was achieved on the basis of the presence or absence of sperm in the ejaculate and further by the concentration of sperm or by testicular score. The levels of plasma LH, FSH, PRL, and T were found to be significantly different in the fertile men, compared with both infertile men with sperm in their ejaculates and azoospermic men. There were no significant differences between the groups for E2. There appeared to be an inverse relationship between LH concentrations and sperm count in both fertile and infertile men. FSH levels did not vary significantly in the fertile men in relation to sperm count grouping but were significantly less than those found for the infertile men with sperm. Azoospermic patients with high testicular scores had FSH levels indistinguishable from those of the fertile men. The results are discussed in terms of testicular abnormalities and on the interrelationship between the hormones examined.

PIP: Plasma concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), testosterone (T), and 17beta estradiol (E2) have been measured in men complaining of infertility in comparison with men with proven fertility. Subgrouping of patients was achieved on the basis of the presence or absence of sperm in the ejaculate and further by the concentration of sperm of by testicular score. The levels of plasma LH, FSH, PRL, and T were found to be significantly different in the fertile men, compared with both infertile men with sperm in their ejaculates and azoospermic men. There were no significant differences between groups for E2. There appeared to be an inverse relationship between LH concentrations and sperm count in both fertile and infertile men. FSH levels did not vary significantly in the fertile men in relation to sperm grouping count but were significantly less than those found for infertile men with sperm. Azoospermic men with high testicular scores had FSH levels indistinguishable which were from those of fertile men. The results are discussed in terms of testicular abnormalities and the interrelationship between the hormones examined.

Tissue-steroid interactions in canine hormone-dependent tumours.

Mammary tumour tissue from two bitches and an anal adenoma from a dog were investigated for steroid receptor interaction. Both mammary tumours possessed cytoplasmic macromolecules sedimenting with coefficients of 4S and 8S that bound oestradiol-17beta. These receptors had molecular weights of approximately 60,000 and 180,000 respectively. Transfer of the oestrogen to the nucleus was shown and the presence of a 4-5S nuclear protein demonstrated. The anal adenoma had a cytoplasmic receptor, with a sedimentation value in a sucrose density gradient of 4-5S with respect to bovine serum albumin, that bound tritiated 5alpha-androstane-3alpha, 17alpha-diol. No affinity could be demonstrated for other C19-steroids examined. The significance of these findings in terms of the hormone dependence of the tumours investigated and the possible development of these studies to promote rational therapy in such cases is discussed.