Regulation of l-ornithine decarboxylase and S-adenosyl-l-methionine decarboxylase in rat ventral prostate and seminal vesicle

1. The activities of l-ornithine decarboxylase (EC 4.1.1.17) and S-adenosyl-l-methionine decarboxylase (EC 4.1.1.50) were dramatically enhanced in both the ventral prostate and the seminal vesicle of castrated rats in response to androgenic stimulation. The time course of the stimulation of ornithine decarboxylase together with the quantitatively different response of adenosylmethionine decarboxylase to testosterone treatment in the prostate gland and seminal vesicle indicated that the enhancement in polyamine synthesis in the ventral prostate may reflect both cellular proliferation and the restoration of the secretory functions of the organ. In the seminal vesicle, however, the stimulation of the polyamine-biosynthetic pathway more closely resembled the pattern found in other rat tissues, such as regenerating liver, undergoing compensatory growth. 2. Ornithine decarboxylase activity in the ventral prostate and especially in the seminal vesicle of sexually mature rat was diminished in vivo by various short-chain diamines such as 1,2-diaminoethane, 1,3-diaminopropane and putrescine (1,4-diaminobutane). These diamines had no direct effect on the enzyme activity in vitro. 3. In contrast with the marginal decrease in ornithine decarboxylase activity produced by diaminoethane in the ventral prostate of non-castrated animals, repeated injections of the latter amine completely prevented the intense stimulation of the enzyme activity in the ventral prostate and seminal vesicle of castrated rats at 24h after the commencement of testosterone treatment. 4. The decrease in ornithine decarboxylase activity observed after injections of diamines (putrescine) in the ventral prostate was apparently associated with a similar decrease in the amount of immunoreactive protein as revealed by immunotitration of the enzyme with antiserum to rat ornithine decarboxylase.     

睾酮对雄家猫附性器官金属硫蛋白的诱导

睾丸切除后,家猫前列腺背叶、腹叶及尿道球腺内的金属硫蛋白（ｍｅｔａｌｏｔｈｉｏｎｅｉｎ,ＭＴ）分别下降至正常家猫的２１２％（Ｐ＜００１）、８８４％（Ｐ＞００５）和１８５％（Ｐ＜００１）,而在腹叶影响较小。睾丸切除后注射芝麻油,前列腺背叶及尿道球腺ＭＴ均未得到恢复。但若在睾丸切除后连续３ｄ注射１０μｇ／ｋｇｂｗ睾酮,两者依次恢复至６９３％和５９４％。随睾酮注射剂量增加（５、１０、１５、２０、２５μｇ／ｋｇｂｗ）,血浆睾酮的浓度、前列腺背叶及尿道球腺ＭＴ含量增高。血浆睾酮与前列腺背叶及尿道球腺ＭＴ呈正相关（Ｐ＜００１）。这些结果表明,睾酮诱导前列腺背叶及尿道球腺ＭＴ,其最适剂量为２０μｇ／ｋｇｂｗ。     

Identification of a novel UDP-Glc:GlcNAc beta1-->4-glucosyltransferase in Lymnaea stagnalis that may be involved in the synthesis of complex-type oligosaccharide chains

Several studies suggest, that the snail Lymnaea stagnalis contains glycoproteins whose oligosaccharide side chains have structural features not commonly found in mammalian glycoproteins. In this study, prostate glands of L. stagnalis were incubated in media containing either [(3)H]-mannose, [(3)H]-glucosamine, or [(3)H]-galactose, and the metabolically radiolabeled protein-bound oligosaccharides were analyzed. The newly synthesized diantennary-like complex-type asparagine-linked chains contained a considerable amount of glucose, next to mannose, GlcNAc, fucose, galactose, and traces of GalNAc. Since glucose has not been found before as a constituent of diantennary N-linked glycans as far as we know, we assayed the prostate gland of L. stagnalis for a potential glucosyltransferase activity involved in the biosynthesis of such structures. We report here, that the prostate gland of L. stagnalis contains a beta1-->4-glucosyltransferase activity that transfers glucose from UDP-glucose to acceptor substrates carrying a terminal N-acetylglucosamine. The enzyme prefers substrates carrying a terminal GlcNAc that is beta6 linked to a Gal or a GalNAc, structures occurring in O-linked glycans, or a GlcNAc that is beta2 linked to mannose, as is present in N-linked glycans. Based on combined structural and enzymatic data, we propose that the novel beta1-->4-gluco-syltransferase present in the prostate gland may be involved in the biosynthesis of Glcbeta1-->4GlcNAc units in complex-type glycans, in particular in N-linked diantennary glycans.     

Age-related changes in the innervation of the prostate gland

The adult prostate gland grows and develops under hormonal control while its physiological functions are controlled by the autonomic nervous system. The prostate gland receives sympathetic input via the hypogastric nerve and parasympathetic input via the pelvic nerve. In addition, the hypogastric and pelvic nerves also provide sensory inputs to the gland. This review provides a summary of the innervation of the adult prostate gland and describes the changes which occur with age and disease. Growth and development of the prostate gland is age dependent as is the occurrence of both benign prostate disease and prostate cancer. In parallel, the activity and influence of both the sympathetic and parasympathetic nervous system changes with age. The influence of the sympathetic nervous system on benign prostatic hyperplasia is well documented and this review considers the possibility of a link between changes in autonomic innervation and prostate cancer progression.     

Age-dependent expression of 5alpha-reductase and androgen receptors mRNA by the canine prostate

The growth of the prostate gland is androgen-dependent. Testosterone is converted to the most potent dihydrotestosterone (DHT) by 5alpha-reductase within the prostate. Androgen interacts with androgen receptors (AR) to regulate normal growth of the prostate and has also been implicated in both the progression of benign prostate hyperplasia and prostate cancer. This study was conducted to compare the mRNA expression of AR and 5alpha-reductase by the prostate gland from three age categories: immature, young-mature and old dogs. Quantitative gene expression was assessed by the real-time PCR and the results were expressed as a relative mRNA expression of the target gene. This study revealed that there was no significant difference in the mRNA expression of the AR gene by the prostate gland of immature, young and old dogs. In contrast, there is a highly significant (P<0.001) down-regulation in 5alpha-reductase gene by the prostate of young and old dogs as compared with immature dogs. However, there is no significant difference in mRNA expression of the 5alpha-reductase gene by the prostate gland from young and old dogs. This differential expression of AR and 5alpha-reductase genes, which are involved in the regulation of androgen effect on prostate gland, might reflect an age-dependent growth requirement of the gland for androgens.     

The androgenic regulation of the activities of enzymes engaged in the synthesis of deoxyribonucleic acid in rat ventral prostate gland.

The restoration of mitosis and growth of the prostate gland of castrated animals by androgens provides a favourable experimental system for studying the hormonal regulation of enzymes engaged in DNA replication. 2. Many DNA polymerase activities were identified in the prostate gland, but only a 9S form with a particular preference for denatured DNA as template was conspicuously enhanced by androgenic stimulation. 3. Thymidine kinase also provided a sensitive indicator of the hormonal regulation of DNA replication, and on electrophoretic criteria, one discrete form of the enzyme appeared precisely with the onset of mitoris. 4. Evidence is presented to support the view that DNA ligase activity is intimately associated in the process of DNA replication in the prostate gland. 5. A spectrum of deoxyribonuclease activities is present in the prostate gland, but only one form (pI7.0) can safely be said to be implicated in the process of DNA replication. 6. Androgenic stimulation of the prostate gland leads to the appearance of a component capable of denaturing or unwinding prostate DNA. This component is seemingly distinct from RNA or DNA polymerase activities on the basis of several distince physicochemical characteristics. 7. The conspicuous feature of all the changes in enzyme activities evoked by androgens in the prostate gland is their acute tissue- and steroid-specificity. Such changes could not be mimicked in liver or spleen and the regulatory role of androgens could not be simulated by other classes of steroid hormones. Particularly on the basis of studies with the anti-androgen cyproterone acetate, it is concluded that the changes are initially mediated by the androgen-receptor system and the high-affinity binding of 5alpha-dihydrotestosterone in the prostate gland. 8. The results are discussed in the context of the mechanism of action of androgens.     

The control of the form and function of the ribosomes in androgen-dependent tissues by testosterone

1. The ribosome content of the rat ventral prostate gland is controlled by the concentrations of circulating androgens and the polyribosomal complement of the total population of ribosomes is acutely dependent on androgenic stimulation. After the administration of testosterone to castrated rats in vivo, there is a pronounced increase in the amounts of heavy (150-240S) polyribosomes. 2. These results are consistent with a pronounced increase in the mRNA and rRNA content of the prostate gland after the administration of testosterone in vivo. 3. From studies conducted both in vitro, the heavy prostate polyribosomes formed after androgenic stimulation are particularly active in protein synthesis. 4. The androgen-stimulated increase in the formation of prostate polyribosomes has a mandatory requirement for sustained RNA and protein synthesis. 5. Since the androgen-mediated increase in prostate polyribosomes may also be suppressed by the concomitant administration of certain anti-androgenic steroids in vivo, the response in polyribosome formation is probably initiated by the binding of a metabolite of testosterone, 5alpha-dihydrotestosterone, in the prostate gland. 6. The relevance of these findings to the pronounced increase in protein synthesis in androgen-dependent tissues after hormonal stimulation is discussed.     

Arguments against the prostatic origin of the R-3327 Dunning H tumor

The Dunning tumor, originally described as a carcinoma of the rat dorsal prostate, has for long been used as an experimental model of prostatic cancer. We have recently presented a number of morphological findings that are incompatible with the prostatic origin of the H-subline of the Dunning tumor. In this paper, biochemical and immunohistochemical markers of rat prostate and mammary gland are studied in the R-3327 Dunning H tumor. Pieces of the H tumor were inoculated in male or lactating female rats. The electrophoretic protein pattern of Dunning tumor extracts was more similar to that of the mammary gland than the dorsolateral prostate. Proteins selectively appearing after metabolic labeling in Dunning tumors grown in lactating rats corresponded to labeled proteins in mammary glands from the same animals. Secretory proteins typical of the lateral prostate (SVS II) and dorsal prostate (transglutaminase) could not be detected immunohistochemically in the Dunning tumor. Western blot studies of tumor extracts and slot blot analysis of RNA preparations from the tumor confirmed the absence of SVS II and prostate specific transglutaminase from the Dunning tumor. On the other hand, the presence of mammary gland proteins such as milk fat globule membrane proteins, lactoperoxidase and lactalbumin were detected in the Dunning tumor by immunohistochemistry and Western blotting, but were absent from the dorsolateral prostate. Transferrin-mRNA, expressed in the male urogenital tract and also in the liver and other tissues, was detected in the mammary gland and Dunning tumor, but not in the dorsolateral prostate. The absence of mammary gland secretory beta-casein in the Dunning tumor was related to the elevated Ha-ras oncogene expression in the tumor, previously reported to suppress casein expression. The findings clearly demonstrate that the prostate cannot be the origin of the Dunning tumor, presently being used in prostatic cancer research. The designation prostatic adenocarcinoma for this tumor is therefore invalid. Furthermore, the data support our view that mammary gland might be the origin of the Dunning tumor, although the derivation from the bulbourethral or the parotid glands cannot strictly be excluded.     

Morphological and histochemical studies on the prostate gland of developing and adult Paramphistomum cervi (Digenea: Paramphistomatidae)

Morphological and histochemical studies have been made on the development of the prostate gland of the digenetic trematode, Paramphistomum cervi during the course of its infection in sheep; histochemical characterization of prostate gland secretion in adult worms and its functional relationship with the transport of spermatozoa have also been studied. In 6-wk-old worms, the terminal portion of the male genital duct is formed of what appears to be a syncytial epithelium containing a relatively large number of nuclei compared to the rest of the male duct. Cellular organization of the prostate gland becomes conspicuous in 8-wk-old worms and the prostate gland is fully developed by 16 wk. Two types of prostate gland cells, characteristic of the adult, become distinct in 16-wk-old worms which contain spermatozoa in the lumen of their vas deferens and pars prostatica. Adult worms show two types of prostate gland cells: type I containing mainly glycoprotein and type II mainly phospholipid granules. Weak-to-strong activities of acid phosphatase, alkaline phosphatase, esterase, lipase, adenosine triphosphatase, tetrazolium reductase, NAD-diaphorase, isocitrate dehydrogenase, glyceraldehyde dehydrogenase, α-glycerophosphate dehydrogenase and glucose-6-phosphate dehydrogenase have been observed in the prostate gland. The release of prostate gland secretion and the passage of spermatozoa through the lumen of pars prostatica appear to be synchronized events.     

Arginine and ornithine decarboxylases, the polyamine biosynthetic enzymes of mung bean seedlings

General properties and relative activities of l-arginine decarboxylase (ADC) (EC 4.1.1.19) and l-ornithine decarboxylase (ODC) (EC 4.1.1.17), two important enzymes in putrescine and polyamine biosynthesis, were investigated in mung bean (Vigna radiata L.) tissues. Both activities increase linearly with increasing concentrations of crude enzyme, but the increase in ADC activity is considerably greater. The decarboxylation reaction is linear for up to 30 to 60 minutes, and both enzymes have a pH optimum of 7.2. alpha-Difluoromethyl-ornithine inhibits ODC activity of excised roots, while increasing ADC activity.High specific activity of both enzymes is detected in terminal buds and leaves, while root and hypocotyl activity is low. Different ADC-to-ODC activity ratios are found in various tissues of mung bean plants. Substantial increase in the activity of both enzymes is detected in incubated sections as compared with intact plants. A comparison of several plant species indicates a wide range of ADC-to-ODC activity ratio.It is suggested that both ADC and ODC are active in plant tissues and that their relative contribution to putrescine biosynthesis is dependent upon the type of tissue and growth process.     

Histology and histochemistry of the accessory reproductive glands in the male hairy-nosed wombat (Lasiorhinus latifrons)

The accessory male reproductive glands of the hairy-nosed wombat, Lasiorhinus latifrons, are a prostate and three pairs of Cowper's glands. Component units of all are branched tubular structures of varying epithelial makeup and secretory content. The prostate has the carrotlike shape and three consecutive regions commonly found in marsupials. The regions differ in their tubular histology and histochemistry: all contain secretory globules in glandular lumina. Cowper's glands A and B are histologically identical except for the absence of interstitial mast cells from gland G: gland C is characterized by narrower tubules and larger epithelial cells. Histochemical tests for protein, carbohydrate and iron indicate that glycogen is a major secretory product of the prostate (largely posterior region), iron is also secreted (mainly posterior region) and a small quantity of acid mucin is produced (mainly central region). Glycogen is a feature also of anterior prostatic glandular epithelium and of the capping cells of the urethral transitional epithelium. Cowper's gland A has considerable protein in its secretion, gland B a neutral glycoprotein and gland C a sialomucin: the latter two also exhibit cytoplasmic glycogen in their secretory cells.     

Histology and histochemistry of the accessory reproductive glands in the male hairy-nosed wombat (Lasiorhinus latifrons)

Summary The accessory male reproductive glands of the hairy-nosed wombat, Lasiorhinus latifrons, are a prostate and three pairs of Cowper's glands. Component units of all are branched tubular structures of varying epithelial makeup and secretory content. The prostate has the carrotlike shape and three consecutive regions commonly found in marsupials. The regions differ in their tubular histology and histochemistry: all contain secretory globules in glandular lumina. Cowper's glands A and B are histologically identical except for the absence of interstitial mast cells from gland B: gland C is characterized by narrower tubules and larger epithelial cells. Histochemical tests for protein, carbohydrate and iron indicate that glycogen is a major secretory product of the prostate (largely posterior region), iron is also secreted (mainly posterior region) and a small quantity of acid mucin is produced (mainly central region). Glycogen is a feature also of anterior prostatic glandular epithelium and of the capping cells of the urethral transitional epithelium. Cowper's gland A has considerable protein in its secretion, gland B a neutral glycoprotein and gland C a sialomucin: the latter two also exhibit cytoplasmic glycogen in their secretory cells.     

Structural changes of the guinea pig prostatic epithelial cells after gossypol treatment

The effect of gossypol acetic acid on the prostate gland of the guinea pig was assessed ultrastructurally. The three lobes of the gland showed differences in sensitivity and reacted differently to gossypol treatment. In the lateral prostate, there was a reduction in the profile of the granular endoplasmic reticulum and dense secretory granules with a concurrent appearance of smaller clear granules and an increase in cytoplasmic filamentous bundles. The latter feature was similar to that of the coagulating gland. In the dorsal prostate, the general reaction was similar to that in the lateral prostate except that there was no increase in filamentous content. In the coagulating gland, there was a reduction or total disappearance of apical secretory blebs and an increase in lysosomes, a feature not found in the lateral and dorsal lobes. Damages to mitochondria were observed in the dorsal prostate and coagulating gland but not in the lateral prostate. It is concluded that gossypol affects not only the testis, but also alters the structure and functions of the prostate gland.     

A genetic screen in Drosophila for regulators of human prostate cancer progression

To uncover the mechanism by which human prostate cancer progresses, we performed a genetic screen for regulators of human prostate cancer progression using the Drosophila accessory gland, a functional homolog of the mammalian prostate. Cell growth and migration of secondary cells in the adult male accessory gland were found to be regulated by paired, N-cadherin, and E-cadherin, which are Drosophila homologues of regulators of human prostate cancer progression. Using this screening system, we also identified three genes that promoted growth and migration of secondary cells in the accessory gland. The human homologues of these candidate genes – MRGBP, CNPY2, and MEP1A – were found to be expressed in human prostate cancer model cells and to promote replication and invasiveness in these cells. These findings suggest that the development of the Drosophila accessory gland and human prostate cancer cell growth and invasion are partly regulated through a common mechanism. The screening system using the Drosophila accessory gland can be a useful tool for uncovering the mechanisms of human prostate cancer progression.     

Proteolytic modification of rat prolactin by subcellular fractions of the lactating rat mammary gland

The current study explored prolactin proteolysis by rat lactating mammary gland. 125I-labelled rat prolactin was incubated with tissue fractions of lactating mammary gland and the extent of prolactin degradation and fragment formation was visualized and densitometrically quantitated from autoradiographs derived from SDS-polyacrylamide gel electrophoresis under reducing conditions. At pH 4.5, the 25 000 X g pellet of mammary gland converted intact prolactin (23 kDa band) to proteolytic fragments (8-16 kDa bands) in a time- and tissue concentration-dependent fashion similar to that reported previously for rat ventral prostate. The prolactin-degrading and -fragmenting activity in lactating mammary gland was 5-10-times that observed for ventral prostate, the most active male tissue. This activity at acid pH was also demonstrable in other fractions of mammary gland but appeared to predominate in the cytosol. The above activities in mammary gland virtually disappeared at pH 7.4, appeared sensitive to aspartate and sulfhydryl proteinase inhibitors, and insensitive to serine and metalloenzyme proteinase inhibitors. The distribution of this activity could not be correlated with a particular enzyme marker. These characteristics of mammary gland activity differed significantly from those reported previously for prostate. When electrophoresis was conducted under non-reducing conditions, prolactin proteolysis in prostate and mammary gland was primarily associated with the formation of a more slowly migrating product (24 kDa band) with little spontaneous 8-16 kDa fragment formation. Re-electrophoresis of the 24 kDa band under reducing conditions resulted in the appearance of the 8 and 16 kDa fragments. In conclusion, prolactin is proteolytically modified by prostate and lactating mammary gland to a variant of intact hormone (24 kDa band) with a cleavage site in its large loop, by two or more widely distributed, acid-dependent proteinases. Lactating mammary gland, the principal target for prolactin, has the capacity to cleave the hormone in its loop at rates higher than any other tissue examined to date.