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Biomedical subjects

S A Shain

Publications and source records attributed to S A Shain.

At least 55 records · Page 3Linked to original sources
PubMed1981

Aging in the AXC rat: differential effects of chronic testosterone treatment on restoration of diminished prostate L-ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase activities.

L-Ornithine decarboxylase (ODC) activity per 100 mg prostate was diminished 88% and S-adenosyl-L-methionine decarboxylase (AMDC) activity similarly ws diminished 57% in the ventral prostate of aged (26-month-old) as compared to that of young (3.8-month-old) AXC rats. Dorsolateral prostate ODC activity was too low to be reliably quantitated. Dorsolateral prostate AMDC activity per 100 mg prostate was diminished 55% in aged AXC rats. The age-related declines in prostate ODC and AMDC were not attributable to changes in the properties of the enzymes in aged AXC rats compared to young rats. There also was no evidence for an age-related production of inhibitors or inactivators of these prostate enzymes. The sensitivities of prostate ODC and AMDC to orchiectomy were comparable in young and aged AXC rats. Treatment of aged AXC rats with exogenous testosterone did not enhance ventral prostate AMDC activity per 100 micrograms DNA, but it did elevate dorsolateral prostate AMDC activity per 100 micrograms DNA to levels indistinguishable from those characteristic of untreated young AXC rats and caused a 303% increase in ventral prostate ODC activity per 100 micrograms DNA. However, ODC activity per 100 micrograms DNA in the ventral prostate of testosterone-treated aged rats was only 49% of that characteristic of untreated young AXC rats. We have identified three categories of age-related changes in prostatic enzyme activity: 1) decline fully reversible by exogenous testosterone, 2) decline partially reversible by exogenous testosterone, and 3) decline not reversible by exogenous testosterone. These alterations may reflect age-related changes in androgen-regulated prostate gene function.

Adenosylmethionine Decarboxylase↗
PubMed1981

Aging in the AXC rat: equivalence of the rates of inactivation of l-ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase in prostate of young and aged rats.

The incorporation of leucine into proteins of ventral and dorsolateral prostates of young (3- to 4-month-old) and aged (24- to 26-month-old) AXC rats was examined in vivo. We established that a single injection of cycloheximide (500 micrograms/100 g BW) maintained 91% (ventral) or 86% (dorsolateral) inhibition of protein synthesis in prostates of young AXC rats and 90% (ventral) or 88% (dorsolateral) inhibition of protein synthesis in prostates of aged AXC rats through at least 120 min post injection. During cycloheximide-maintained inhibition of protein synthesis, the rate of inactivation of ventral prostate L-ornithine decarboxylase (ODC) or S-adenosyl-L-methionine decarboxylase (AMDC) activity and dorsolateral prostate AMDC activity was comparable in the prostates of young and aged AXC rats. The absence of an age-related change in the rate of inactivation of prostatic ODC or AMDC activity provides additional evidence that the age-related decrease in prostatic ODC and AMDC activities reported in the companion article may reflect altered androgen regulation of prostatic gene activity.

Adenosylmethionine Decarboxylase↗
PubMed1981

A x C rat prostate adenocarcinoma: initial characterization of testosterone regulation of hormone receptors of cultured cancer cells and derived tumors.

A x C rat prostate cancer cells were established in continuous culture. The polygonal epithelial cells had granular cytoplasm and well-defined cell margins, contained round to oval nuclei with prominent nucleoli, and were tumorigenic when inoculated into A x C male rats. The tumors produced by the injected prostate cancer cells grew as well-vascularized, solid, cribriform adenocarcinomas. The rat prostate cancer cells and derived tumors contained cytoplasmic and nuclear androgen receptors and prolactin receptors. Androgen regulation of prolactin receptor content and androgen receptor distribution in A x C rat prostate cancer cells were comparable to those of the normal ventral prostate gland. These studies suggest that the A x C rat prostate cancer cells and tumors may represent a unique model for studies of hormonal regulation of prostate cancer cell behavior.

Adenocarcinoma↗
PubMed1980

Androgen regulation of androgen receptor content and distribution in the ventral and dorsolateral prostates of aging AXC rats.

Total androgen receptor content of ventral or dorsolateral prostate of intact, aged (730-740 day old) rats is decreased 50% when compared to intact, young mature (150-170 day old) rats. Treatment with exogenous testosterone increased ventral and dorsolateral prostate androgen receptor content per cell in aged rats to values identical to those of prostates of young mature rats. The increase in prostate receptor content was not attributable to testosterone mediated cellular hypertrophy or hyperplasia. At 24 hr post-orchiectomy ventral prostate cytoplasmic androgen receptors are depleted of endogenous androgen, without any decrease in number of receptors per cell, and nuclear androgen receptors are undetectable. During 30 to 60 min after a single 200 microgram testosterone injection, ventral prostate nuclear receptor content increased to the level of intact control rats without producing any reduction in total cytoplasmic androgen receptor content. Although dorsolateral prostate is devoid of cytoplasmic androgen receptor, the effects of orchiectomy and testosterone treatment upon nuclear androgen receptor are comparable to those seen in ventral prostate. These effects of orchiectomy and testosterone injection upon prostatic receptor content and distribution were identical in prostates of young and aged rats. Our studies show that receptor processing in prostates of young and aged rats does not involve a process by which nuclear receptor is derived by depletion of cytoplasmic receptor. Moreover, our studies of the effect of short-term (48 hr) exogenous testosterone treatment upon androgen receptor content in prostates of aged rats are the first demonstration that androgen receptor content may be enhanced independent of generalized androgen mediated anabolic effects in prostate.

Aging↗
PubMed1979

Testosterone metabolism by the prostate of the aging AXC rat.

Testosterone metabolism by the ventral prostate of inbred, senescent (36-month-old) AXC rats showed a shift to increased oxidative and diminished reductive metabolism when compared to young mature (3-month-old) or mature adult (6-month-old) AXC rats. The change was principally attributable to diminished production of 5 alpha-dihydrotestosterone and increased production of 4-androstenedione. By contrast, dorsolateral prostate testosterone metabolism in these same rats was always more reductive than that of ventral prostate and failed to show the post-maturation shift to oxidative testosterone metabolism which characterized ventral prostate. Co-incubation of either ventral or dorsolateral prostate from any of these rats with testosterone and estradiol showed that estradiol did not significantly affect prostate testosterone metabolism. Plasma testosterone content of senescent AXC rats was only 28% of that of mature adult rats. Chronic exogenous testosterone treatment enhanced reductive testosterone metabolism by ventral prostate and eliminated those changes in metabolite distribution which had differentiated testosterone metabolism by young and senescent AXC rats. The data support the interpretation that the aging-related diminution in AXC rat ventral prostate reductive metabolic capacity is primarily the consequence of diminished 5 alpha-dihydrotestosterone production secondary to diminished plasma testosterone content.

Aging↗
PubMed1979

Testosterone metabolism by the prostate of the aging canine.

Examination of testosterone metabolism in the dorsal, lateral, and ventral regions of the beagle prostate showed an absence of regional heterogeneity for testosterone metabolite production and metabolic capacity. Testosterone metabolism by the hyperplastic prostate of aged beagles (11.1 years old) was distinguished from that of young mature (2.5-year-old) and mature adult (4.5-year-old) beagle prostate by increased reductive metabolism. The change was principally the consequence of increased production of 5 alpha-dihydrotestosterone and decreased production of 4-androstenedione. These alterations in testosterone metabolism occurred progressively and may be weakly linked to other changes in canine prostate which occur during aging. 5 alpha-Androstane-3 alpha, 17 beta-diol production was maximal for prostate from 4.5-year-old beagles and the amount of this metabolite produced appeared to be unrelated to prostate size. Co-incubation of prostate from any of the beagles with testosterone and estradiol showed that estradiol had no in vitro effect upon testosterone metabolism. Mean plasma testosterone content of aged beagles (11.1 years old) was not significantly different from that of younger individuals; however, the heterogeneity of the values for the subject groups was notable. The data demonstrate that the consequences of aging upon testosterone metabolism by canine prostate, which principally develops benign prostatic hyperplasia, are opposite to those characteristic of senescent rat prostate, which does not develop bening prostatic hyperplasia and has a high incidence of spontaneous adenocarcinoma.

Aging↗
PubMed1978

Characterization of unoccupied (R) and occupied (RA) androgen binding components of the hyperplastic human prostate.

Saturation protocols were developed for measurement of unoccupied (R) and steroid-occupied (RA) androgen binding components of human hyperplastic prostate. The concentration of unoccupied cytoplasmic binding sites (2 hr incubation at 2 degrees C) for the synthetic androgen R1881 (17beta-hydroxy-17alpha-methyl-estra-4,9,11-trien-3-one) and the synthetic progestin R5020 (17alpha,21-dimethyl-19-norpregna-4,9-diene-3,20-dione) respectively was 10.7 +/- 1.4 and 14.3 +/- 3.2 fmoles per mg cytosol protein and the apparent steroid affinity respectively was 9.6 +/- 0.8 and 1.6 +/- 0.4 x 10(8) M-1. Steroid specificity of the unoccupied cytoplasmic R1881 and R5020 binding sites was similar. When R1881 and R5020 were employed as probes of total, R plus RA, cytoplasmic binding components (20-24 hr incubation at 15 degrees C) saturable binding of R5020 was not detectable. Total cytoplasmic R1881 binding site concentration and apparent affinity for R1881 were 51.7 +/- 3.3 fmoles per mg cytosol protein and 2.7 +/- 0.6 x 10(7) M-1. R5020 was a poor inhibitor of R1881 binding to total cytoplasmic R1881 binding components.

Binding Sites↗
PubMed1978

Androgen receptor content of the normal and hyperplastic canine prostate.

A procedure was developed for measurement of androgen receptors in cytoplasmic extracts of prostates from intact dogs. The protocol utilized exchange saturation analysis at 15 degrees C employing the synthetic androgen R1881 (17beta-hydroxy-17alpha-methylestra-4,9,11-trien-3-one) as the ligand probe and quantitatively detected total cytoplasmic androgen receptor (R(c), androgen-free receptor, and R(c)A, androgen-occupied receptor) present at the initiation of the assay. This protocol was employed in conjunction with a tissue mince saturation analysis procedure (for quantitation of nuclear androgen receptor) to quantitate total androgen receptor content of normal and hyperplastic prostates obtained from young (2.5- or 4.6-yr old) and aged (12.5-yr old) purebred dogs of known birth date. The total cytoplasmic androgen receptor content (picomoles per prostate) of hyperplastic prostates was 4.6-fold greater than that of normal prostates. The total nuclear androgen receptor content of hyperplastic prostates (picomoles per prostate measured in crude nuclear preparations) was either 5.0- (4.6-yr-old dogs) or 7.8-fold (2.5-yr-old dogs) greater than that of normal prostates. However, androgen receptor content per cell was identical for hyperplastic and normal canine prostates, with the exception that nuclear androgen receptor was diminished in prostates from 2.5-yr-old dogs. The cell content per gram dry weight was identical for hyperplastic and normal canine prostates. We conclude that canine prostate hyperplasia is characterized by coordinate proliferation of androgen receptor-positive and androgen receptor-negative cells and is not a consequence of increased accumulation of 5alpha-dihydrotestosterone due to proliferation of androgen receptors per prostate cell.

Aging↗
PubMed1977

C19-steroid metabolism by spontaneous adenocarcinoma of the A X C rat ventral prostate.

Specimens of ventral prostate from 37- to 46-month-old Andradurin-treated A X C rats demonstrated three primary morphologic patterns, each being divisible into two sub-groups based upon the extent of glandular alteration. The principal groups were: group 1, hyperplasia; group 2, atypical hyperplasia; and group 3, adenocarcinoma. The secondary classifications were: subgroup (+), few glands involved; and subgroup (++), most glands involved. Multiple parameters of ventral prostate testosterone metabolic potential failed to distinguish the morphologically diverse prostate specimens of groups (1+). 1(++), 2(+), 2(++), and 3(+) which predominantly metabolized testosterone to 5alpha-reduced 17beta-hydroxysteroids. By contrast, testosterone metabolism by ventral prostate specimens predominantly composed of neoplastic epithelium, group 3(++), was distinct from all other prostate specimens. The distinguishing feature was a shift to more prominent elaboration of 17-ketosteroids, principally delta4-androstenedione, and a cteroids. The change in this biochemical parameter of prostate epithelial cell function was indicated to be an early manifestation of the neoplastic transformation.

17-Ketosteroids↗