Protocatechuic acid ameliorates testosterone‐induced benign prostatic hyperplasia through the regulation of inflammation and oxidative stress in castrated rats

Protocatechuic acid (PA) is a polyphenol—recognized for its efficacy as an antioxidant—possesses anticancer, anti‐inflammatory, antioxidant properties. The efficacy of PA in the management of benign prostatic hyperplasia (BPH) has not been investigated. Forty‐two castrated rats (n = 7) were treated as follows: control (corn oil), BPH only received testosterone propionate (TP) (TP 3 mg/kg intraperitoneally), BPH + PA (TP 3 mg/kg + PA 40 mg/kg), BPH + finasteride (Fin) (TP 3 mg/kg + Fin 10 mg/kg), PA only (40 mg/kg: by gavage), and Fin only (10 mg/kg: by gavage) for 4 weeks. In BPH rats, there were significant (P < .05) increases in prostatic (250%) and organosomatic (280%) weights compared with controls. Cotreatment decreased prostatic weights by 19% (PA) and 21% (Fin). Markers of inflammation: myeloperoxidase activities increased in serum (148%) and prostate (70%), as well as nitric oxide levels serum (92%) and prostatic (95%). Proinflammatory cytokines interleukin‐1β and tumor necrosis factor‐α increased by 3.6‐ and 2.8‐fold. Furthermore, prostatic malondialdehyde, superoxide dismutase, and serum total acid phosphatase increased by 97%, 25%, and 48%, respectively. Histology revealed poor architecture and severe proliferation of the prostate in BPH rats. Inflammation and oxidative stress markers, as well as the histological alteration in BPH rats, was attenuated (P < .05) upon cotreatment with PA and comparable with Fin cotreatment. These results suggest that PA mitigates oxido‐inflammatory responses and restored prostatic cytoarchitecture to levels comparable with control in rats induced with BPH.     

Hormone-independent polyamine metabolism of squamous cell carcinoma of the prostate

The levels of polyamines and their synthesizing enzymes in squamous cell carcinoma of prostate implanted in intact as well as castrated male rats were determined after certain hormonal manipulations. The tumour was found to grow with an identical rate in non-castrated and castrated rats. Polyamine content and activities of polyamine synthesizing enzymes in the tumour were found to be much lower compared to their values in ventral prostate. Moreover, the levels of these parameters were comparable in tumours whether implanted in non-castrated or gonadectomized animals. The sequential analyses of putrescine and spermidine and activities of L-ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase of tumours at different time intervals showed a significant reduction in their levels at 30 days compared to 10 days post implantation in non-castrated as well as castrated rats. Daily intramuscular administration of tumour-bearing intact or castrated animals with testosterone (50 micrograms/g), beta-estradiol (2 micrograms/g) or cyproterone (12.5 micrograms/g) for 10 days did not influence polyamine metabolism in tumour tissue. However, either beta-estradiol and cyproterone treatments or castration were found to decrease polyamine synthesis in ventral prostate. At the same time, the testosterone replacement therapy did not allow polyamine levels or activities of polyamine synthesizing enzymes to decline in the ventral prostate of castrated rats. Our results demonstrated that contrary to ventral prostate, the polyamine metabolism in squamous cell carcinoma of prostate is independent of hormonal control. The loss of hormonal sensitivity of polyamine metabolism in the prostatic tumour could be the result of qualitative changes that occurred during transformation.     

Effect of sorghum ethyl-acetate extract on benign prostatic hyperplasia induced by testosterone in Sprague–Dawley rats

ABSTRACT

Benign prostatic hyperplasia (BPH) is commonly observed in men > 50 years worldwide. Phytotherapy is one of the many treatment options. Sorghum (Sorghum bicolor L.) contains various health-improving phytochemicals with antioxidant and inhibitory activities on cell proliferation, both in vitro and in vivo. To confirm the effects of Donganme sorghum ethyl-acetate extract (DSEE) on BPH, we induced BPH in Spragye–Dawley rats using exogenous testosterone. We measured prostate weight, examined prostrates histopathologically, and analyzed mRNAs associated with male hormones and proteins associated with cell proliferation in the prostate. DSEE inhibited weight gain of the prostate; decreased mRNA expressions of androgen receptor and 5α-reductase II; and improved histopathological symptoms, the protein-expressed ratio of Bax/Bcl-2, and the oxidative status of BPH induced by testosterone in SD rats. Therefore, DSEE may have potential as a preventive or therapeutic agent against BPH.     

Relative influence of testosterone and insulin in the regulation of prostatic cell proliferation and growth

Prostatic hyperplasia is a common problem of the aged men population. Recent experimental and clinical studies provide sufficient evidence that apart from androgens, insulin also plays an important role in the pathogenesis of prostatic hyperplasia. The present study was aimed to investigate the relative influence of testosterone and insulin on the cellular proliferation and prostatic growth. Effect of testosterone on the prostate of hypoinsulinemic, and glandular injection of insulin-receptor antagonist S961 on the prostate of castrated Sprague-Dawley rat (220 ± 10 g) was examined. Significant decrease in the weight of the ventral prostate was observed in the streptozotocin-induced hypoinsulinemic rats (∼6 fold), which is restored by the intervention of testosterone. Although, glandular injection of S961 did not led to any change in the frequency of proliferating cell nuclear antigen (PCNA) positive cells in normal rats, significant decrease was observed in the castrated rats. Castration led to increase in the frequency of the caspase-3 and the TUNEL positive cells in the ventral prostate. Further, long-term (6 weeks) administration of S961 induced significant decrease in the weight of the ventral prostate. Results of the present study provide that both testosterone and insulin promote prostatic cell proliferation and change in the level of either of the hormone results in the destabilization of cellular equilibrium, and modulation of the insulin-receptor signaling in the prostate may provide an alternative strategy for the treatment of prostatic enlargement. Further, studies are required to better understand the interplay between these hormones in the regulation of prostatic growth.     

New quantification method for estradiol in the prostatic tissues of benign prostatic hyperplasia using liquid chromatography-tandem mass spectrometry

Estrogen is suspected to play a role in the pathogenesis of benign prostatic hyperplasia (BPH) and prostate cancer. To clarify the role of estradiol (E2) in the prostatic tissues (prostatic tissue E2) during the development of prostatic disorders, we developed a new sensitive and specific quantification method for prostatic tissue E2 using liquid chromatography-tandem mass spectrometry (LC-MS/MS). For the solid-phase extraction, E2 was purified by anion-exchange through an Oasis MAX cartridge. In addition, after the formation of 3-pentaflurobenzyl-17β-pyridinium-estradiol derivative (E2-PFBPY), E2-PFBPY was purified by cation-exchange through an Oasis WCX cartridge. These processes in the LC-MS/MS method improved the specificity and sensitivity for prostatic tissue E2 measurement, compared to the radioimmunoassay (RIA) method. The validation tests showed that intra-day and inter-day precisions were both within ±15% (except for 15.5% of the inter-day precision of the lowest concentration), with the accuracy ranging from 88 to 110%. The quantification limit of this assay was 0.15 pg/tube in our method, which was 80-fold more sensitive than that of the RIA method. With the use of our present method, the median E2 levels in the prostatic tissues in patients with BPH (n = 20, median age: 71 years) were 12.0 pg/g tissue (95% confidence interval = 9.1-22.6 pg/g tissue). Furthermore, the E2 levels increased significantly with aging. These results showed that our present method would be useful for elucidating the role of prostatic tissue E2 in the development of prostatic disorders with a small amount of tissue samples.     

Effects of Testosterone on Triglyceride Uptake and Mobilization in Different Adipose Tissues in Male Rats in Vivo

LI, MIN AND PER BJ4OURNTORP. Effects of testosterone on triglyceride uptake and mobilization in different adipose tissues in male rats in vivo. Obes Res. 1995;3:113–119. The effects of testosterone (T) on uptake and mobilization of orally administered triglyceride were examined in male rats. In order to attempt to explain regional differences, adipose tissue metabolism was studied in vivo. (U-14 C) oleic acid in sesame oil was given by gastric gavage to male, sham operated, castrated and castrated + T substituted rats, and accumulation and half-life of radioactivity measured. In castrated rats in comparisons with sham-operated and castrated + T rats, serum T was absent, and body weight lower (P< 0.05 or 0.01), but adipocytes in retroperitoneal and mesenteric tissues became significantly heavier. Radioactivity (dpm/mg triglyceride) was higher, in retroperitoneal tissue at 4 hours, 7, 30 days, and in mesenteric tissue at 4 hours, and at 30 and 60 days after oral label administration (0.1 > p > 0.05 or P< 0.05), no differences were seen in epididymal or inguinal depots at 4 hours. When radioactivity was expressed per adipocyte, the castrated group showed significantly higher radioactivity when compared to sham and castrated + T groups at 7 and 30 days in retroperitoneal and at 60 days in mesenteric adipocytes (P< 0.05 or 0.01). Half life (T 1/2) of radioactivity was longer in mesenteric tissue in the castrated rats than the other two groups (sham group, 33 days ± 2; castrated group, 58 days ± 6; and castrated + T group, 39 days ± 3, P< 0.05), but there were no differences between groups in retroperitoneal adipose tissue. It was concluded that T exerts important, multiple effects on triglyceride storage and mobilization in adipose tissue, with regional differences between adipose tissues.     

Saw Palmetto Berry as a Treatment for BPH

Phytotherapeutic agents are often prescribed in Europe for the treatment of benign prostatic hyperplasia with lower urinary tract symptoms and are commonly used in the United States in over-the-counter preparations. Saw palmetto berry is the most popular of these agents, and in vitro some studies suggest that liposterolic extract of the plant has antiandrogenic effects that inhibit the type 1 and type 2 isoenzymes of 5alpha-reductase; however there are no clinical studies that show any decrease in serum dihydrotestosterone or prostate-specific antigen. Its efficacy in the treatment of lower urinary tract symptoms has not been conclusively proven. Clinical efficacy was suggested by a meta-analysis of Permixon, a formulation of saw palmetto, but the meta-analysis was done on suboptimal studies. One trial supports the equivalency of Permixon to finasteride in treating moderate to severe symptoms of benign prostatic hyperplasia, with less decrease in sexual function. However, without a control/placebo arm, the actual efficacy of the agents cannot be determined. Other than occasional gastrointestinal upset, no other side effects have been reported.     

The anti-inflammatory properties of the methanolic extract of Cucumis melo Linn. against prostate enlargement in Wistar rats

In different parts of the world, Cucumis melo Linn. (C melo) is used for its medicinal properties. The present study examined the effects of a methanolic extract of C melo Linn. (F1 hybrid, MECM) on benign prostatic hyperplasia in adult male Wistar rats and evaluated its anti-inflammatory activity in vivo. MECM treatment reduced prostate weight mildly. Histopathological studies showed that the extract produced a strong protective effect against the development of BPH by testosterone. The MECM also showed protection from testosterone-induced benign prostatic hyperplasia (BPH). MECM was tested against carrageenan-induced inflammation in rats' paws to determine its anti-inflammatory activity. It was shown that MECM had a pronounced effect on the inflammatory response in the late phase, i.e., one hour after carrageenan injection. Prostaglandins and nitric oxide are primarily responsible for this phase indicating that MECM can modify the production and release of prostaglandin and nitric oxide. A novel formulation containing C melo may be able to treat the conditions mentioned above.     

Some effects of testosterone on the rat ventral prostate

1. Labelled testosterone, injected directly into the ventral prostate of castrated rats became associated, in part, with a cytoplasmic high-molecular-weight fraction, fraction ;A'. 2. The label present in fraction ;A' was found to be mainly associated with dihydrotestosterone. 3. Unlike fraction ;A' from testosterone-pelleted castrated rats, fraction ;A' obtained from untreated castrated rats, 48h or more after castration, was strongly inhibitory towards Escherichia coli RNA polymerase in vitro. 4. The inhibition of RNA polymerase by fraction ;A' from castrated rats was not changed by the addition of testosterone or dihydrotestosterone in vitro, but pre-heating it to 80 degrees C resulted in a loss of its inhibitory capacity. 5. Fraction ;A' from castrated rats contained ribonuclease activity. The elution profile of ribonuclease activity from Sephadex columns indicated that this activity was responsible for the inhibitory effect on the RNA polymerase assays. 6. It is concluded that, unlike the inhibitor present in the uterus of ovariectomized rats (Talwar, Segal, Evans & Davidson, 1964), no direct connexion exists between the steroid-binding capacity of prostatic fraction ;A' and its effect on E. coli RNA polymerase activity in vitro.     

Dose–response effect of Red Maca (Lepidium meyenii) on benign prostatic hyperplasia induced by testosterone enanthate

The main goal of this study was to determine the effect of a freeze-dried aqueous extract of the red variety of Lepidium meyenii (Red Maca) on testosterone-induced benign prostatic hyperplasia (BPH) in adult rats of the Holtzman strain. Rats were treated with freeze-dried aqueous extract of Red Maca at doses of 0, 0.01, 0.05, 0.1, and 0.5 g/kg body wt. A positive control group received Finasteride (0.6 mg/kg body wt.). After treatment, the animals were sacrificed, and the ventral prostate was extracted, and weighed. HPLC was used to determine the presence of glucosinolates in Red Maca. The prostate weight diminished in a dose-dependent fashion in rats treated with Red Maca. The effect of Red Maca was better than that observed with Finasteride. Finasteride, but not Red Maca, reduced seminal vesicles weight. Analysis of the HPLC indicated the presence of benzyl glucosinolate (Glucotropaeolin) with a content of 0.639%. Serum testosterone levels were not affected by Red Maca. Moreover, serum testosterone levels were not related to prostate or seminal vesicles weight in rats treated with vehicle and Red Maca. In conclusion, Red Maca administered orally in rats seems to exert an inhibitory effect at a level post DHT conversion, on the BPH-induced experimentally, although a direct measure of reductase action would still be required.     

Effects of Panax ginseng on the nerve growth factor expression in testosterone induced benign prostatic hyperplasia

The prostatic hyperplasia in benign prostatic hyperplasia (BPH) leads to obstructive micturition symptoms. Previous studies showed that pontine micturition center (PMC), ventrolateral periaqueductal gray (vlPAG), and medial preopticnucleus (MPA) regions in the brain have been known to regulate the urinary bladder function. The present study shows the influences of Panax ginseng on nerve growth factor (NGF) expressions in PMC, vlPAG, and MPA regions in the brain. Wistar rats were used for the present study. The rats split into four groups; 4 groups (n = 6) in control group, BPH-induced group, BPH-induced and P. ginseng-treated group, and BPH-induced and finasteride-treated group. BPH in rats was induced by testosterone and the animals were evaluated for NGF expression in PMC, vlPAG, and MPA regions in the brain. The NGF expression was identified using immunohistochemistry (IHC). The NGF expression by IHC showed spots with dark brown color. In our results, NGF expressions in PMC, vlPAG, and MPA regions in the brainstem of the BPH-induced group showed increase than the control animal. These increased NGF expressions in three regions were decreased using treatment with P. ginseng (200 mg/kg). These results suggest that P. ginseng has therapeutic effects on the symptoms of BPH and is associated with the regulation of NGF expression in the brain. In conclusion, the administration of P. ginseng helps nerve growth factor activation.     

Selenium in combination with a tomato lipid extract as a therapy for benign prostatic hyperplasia and its alterations in rats with induced BPH

Benign prostatic hyperplasia (BPH) is the most common adenoma in old men. Tomatoes are a rich source of bioactive compounds that, as well as selenium (Se), possess antioxidant and antiproliferative activity. The aim was to evaluate the therapeutic effect of Se in combination with a tomato extract in aged rats with BPH. Aged male Wistar rats were divided in the following groups (n = 10 rats/group): Control (C), BPH, BPH + Finasteride (BPH + F), BPH + Tomato Lipidic Extract (BPH + E), BPH + Selenium (BPH + S) and BPH plus E plus S (BPH + E + S). After 4 weeks of treatment, prostate weight, diuresis, antioxidants enzymes, prooxidants and inflammatory markers, growth factors and androgens were determined. BPH + E + S reduced prostate weight by 59.29% and inhibited growth by 99.35% compared to BPH + F which only decreased weight and inhibited growth by 15.31% and 57.54%, respectively. Prooxidant markers were higher with BPH + F (49.4% higher vs. BPH), but BPH + E + S decreased these markers (94.27% vs. BPH) and increased antioxidant activity. Finally, diuresis was higher with the BPH + E + S combination and markers of inflammation and growth factors were significantly lower with respect to BPH + F. Our findings provide a beneficial and protective therapeutic option of E + S directed against androgens, oxidative stress and inflammation that regulates cell proliferation in the prostate gland.     

Effects of 5α-reductase inhibitors on intraprostatic androgens in the rat

FCE 27837 is a novel inhibitor of 5α-reductase, the enzyme responsible for the conversion of testosterone (T) to 5α-dihydrotestosterone (DHT). The compound caused inhibition of human and rat prostatic enzymes, with IC₅₀ values of 51 and 60 nM, respectively. The in vivo effect of FCE 27837 on 5α-reductase was evaluated in adult male rats, treated orally at 10 mg/kg/day for 10 days. The compound caused 33 and 42% reductions in ventral prostate and seminal vesicle weights, respectively. The prostatic content of DHT, measured 6 h after the 10th dose of FCE 27837, was reduced by 75%, whereas T content increased by 442%. Similar effects were observed with 10 mg/kg/day of finasteride, whereas epristeride, tested at the same oral dose, was found to be the least effective compound, decreasing prostate weight by 22% and DHT content by 46%. Castration caused >90% reductions in prostatic weight and prostatic DHT.     

Testosterone selectively increases serum follicle-stimulating hormonal (FSH) but not luteinizing hormone (LH) in gonadotropin-releasing hormone antagonist-treated male rats: evidence for differential regulation of LH and FSH secretion

Both testosterone (T) and gonadotropin-releasing hormone (GnRH)-antagonist (GnRH-A) when given alone lower serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in intact and castrated rats. However, when graded doses of testosterone enanthate (T.E.) were given to GnRH-A-treated intact male rats, a paradoxical dose-dependent increase in serum FSH occurred; whereas serum LH remained suppressed. This surprising finding led us to ask whether the paradoxical increase in serum FSH in GnRH-A-suppressed animals was a direct stimulatory effect of T on the hypothalamic-pituitary axis or the result of a T effect on a testicular regulator of FSH. To test these hypotheses, we treated adult male castrated rats with GnRH-A and graded doses of T.E. In both intact and castrated rats, serum LH remained undetectable in GnRH-A-treated rats with or without T.E. However, addition of T.E. to GnRH-A led to a dose-dependent increase in serum FSH in castrated animals as well, thus pointing against mediation by a selective testicular regulator of FSH. These data provide evidence that pituitary LH and FSH responses may be differentially regulated under certain conditions. When the action of GnRH is blocked (such as in GnRH-A-treated animals), T directly and selectively increases pituitary FSH secretion.     

Development, survival and fecundity of the urine fly, Scatella (Teichomyza) fusca and predation by the black dumpfly, Hydrotaea aenescens

Development, survival and fecundity for Scatella (Teichomyza) fusca Maquart (Diptera: Ephydridae) were studied at 20 ± 1 °C and 85 ± 10% r.h. Mean (± S.E.) developmental times of eggs, larvae and pupae were 4.0 ± 0.06, 14.9 ± 0.19 and 14.6 ± 0.11 days, respectively, the mean (± S.E.) survival of the original egg cohort to the start of larval, pupal and adult stage being 77.2 ± 3.2%, 54.5 ± 2.6% and 47.9 ± 3.5%, respectively. Females and males displayed approximately straight survivorship curves during adult life, implying constant mortality rates. Mean (± S.E.) adult longevity was 41.6 ± 2.98 days for females and 51.2 ± 3.91 days for males. Assuming a stable age distribution the population consisted of 56% eggs, 31% larvae, 6% pupae and 7% adults. Oviposition peaked when females were 25 days old, and the highest reproductive values (RV_x) (mean ± S.E.) ranged from 129.1 ± 7.57 to 138.5 ± 6.83 for individuals 17–27 days old. A female deposited a mean (± S.E.) of 614.7 ± 35.9 female eggs over a maximum life span of 93 days. The basic reproductive rate (R ₀) (mean ± S.E.) was 173.0 ± 14.2 female offspring per female and the intrinsic rate of natural increase of female individuals (r) (mean ± S.E.) was 0.088 ± 0.001 day^-1. The mean (± S.E.) generation time (T) was 57.8 ± 0.78 days. In cultures with equal numbers of first instar S. fusca larvae and predacious third instar larvae of Hydrotaea aenescens (synonymous Ophyra aenescens) Wiedemann, mean (± S.E.) survival to the adult stage of S. fusca (16.7 ± 8.8%) was significantly lower than in controls with S. fusca alone (58.3 ± 7.4%). The potential significance of predation by H. aenescens on S. fusca in pig farms is discussed.     

Differential effect of 5 alpha-reductase inhibition and castration on androgen-regulated gene expression in rat prostate.

Castration reduces prostate size and causes intraprostatic testosterone (T) and dihydrotestosterone (DHT) to fall to very low levels. 5 alpha-Reductase inhibition also reduces prostate size, but results in a marked increase in intraprostatic T levels. To compare the effects of 5 alpha-reductase inhibition and castration on prostate physiology, male Sprague-Dawley rats were left intact, castrated, or given the selective 5 alpha-reductase inhibitor finasteride for up to 9 days. To be sure that finasteride itself did not directly affect gene expression, an additional group of rats was castrated and given finasteride for 4 days. The prostates were weighed, intraprostatic RNA, DNA, and androgen levels were measured, and mRNAs for two androgen-regulated genes, prostate steroid-binding protein (PSBP; an androgen-induced gene) and testosterone-repressed prostate message (TRPM-2), were quantitated by Northern and slot blot analyses. Finasteride caused a 95% reduction in intraprostatic DHT levels and a 10-fold increase in intraprostatic T levels. Finasteride, as expected, caused a pronounced decrease in prostate weight (45% on day 4). DNA content fell correspondingly (48% on day 4). Intraprostatic DNA (micrograms of DNA per gland) on day 4 was 328 +/- 53 in control rats, 171 +/- 10 in finasteride-treated rats (P less than 0.001 compared to controls), 115 +/- 2 in castrated rats (P less than 0.05 compared to finasteride), and 107 +/- 43 in finasteride-treated plus castrated rats (P = NS compared to castration alone). There were no significant differences in DNA levels among the groups when expressed per mg prostate tissue, indicating that mean prostate cell size was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Selenium level in benign and cancerous prostate

The dietary microelement selenium (Se) has been proposed as a potential chemopreventive agent for prostate cancer. This element is present in various amounts in all tissues. Little information is available on Se level in patients with prostate gland disorders. The levels of Se in prostatic gland of patients with prostate cancer, benign prostate hyperplasia, and healthy controls were examined. The Se level for benign prostate hyperplasia (156±30.6 ng/g) was the same as in the control group (157±26.0 ng/g), but in the gland of prostate cancer patients (182±34.1 ng/g wet weight), the Se level was significantly (p<0.01) higher than in both healthy controls and benign prostate hyperplasia. Thus, the Se level in human healthy controls is lower than in kidney and liver but higher compared with other tissues.     

The Influence of Sex Steroid Hormones in the Immunopathology of Experimental Pulmonary Tuberculosis

The relation between men and women suffering pulmonary tuberculosis is 7/3 in favor to males. Sex hormones could be a significant factor for this difference, considering that testosterone impairs macrophage activation and pro-inflammatory cytokines production, while estrogens are proinflammatory mediator’s inducer. The aim of this work was to compare the evolution of tuberculosis in male and female mice using a model of progressive disease. BALB/c mice, male and female were randomized into two groups: castrated or sham-operated, and infected by the intratracheal route with a high dose of Mycobacterium tuberculosis strain H37Rv. Mice were euthanized at different time points and in their lungs were determined bacilli loads, inflammation, cytokines expression, survival and testosterone levels in serum. Non-castrated male mice showed significant higher mortality and bacilli burdens during late disease than female and castrated male animals. Compared to males, females and castrated males exhibited significant higher inflammation in all lung compartments, earlier formation of granulomas and pneumonia, while between castrated and non-castrated females there were not significant differences. Females and castrated males expressed significant higher TNF-α, IFN γ, IL12, iNOS and IL17 than non-castrated males during the first month of infection. Serum Testosterone of males showed higher concentration during late infection. Orchidectomy at day 60 post-infection produced a significant decrease of bacilli burdens in coexistence with higher expression of TNFα, IL-12 and IFNγ. Thus, male mice are more susceptible to tuberculosis than females and this was prevented by castration suggesting that testosterone could be a tuberculosis susceptibility factor.     

Short- and long-term effects of testosterone on diaphragm in castrated and normal male rats

Prezant, David J., Manoj L. Karwa, Helen H. Kim, DianeMaggiore, Virginia Chung, and David E. Valentine. Short- and long-term effects of testosterone on diaphragm in castrated and normalmale rats. J. Appl. Physiol. 82(1):134-143, 1997.The effects of short- and long-term testosteroneabsence or treatment on the diaphragm were studied in castrated andsexually normal male rats. Compared with control rats (untreated normalmales), testosterone absence or treatment did not significantly affect costal weight. In untreated castrated males, there were significant decreases in specific forces, type II fiber cross-sectional area, andmyosin heavy chain (MHC) isoform 2B after 2.5 wk. In castrated malesthat received testosterone, there were significant increases inspecific forces, type II total fiber proportional area, and relativeexpression of all adult diaphragm fast MHC isoforms(MHC-2_all) after 2.5 wk. In normal males thatreceived testosterone, the only significant finding was an increase inMHC-2B after 2.5 wk. Across all groups, there was close correlationbetween increases in maximum tetanic forces and MHC-2_all.Changes in diaphragm function and composition were closely related tochanges in serum testosterone levels at 2.5 wk. The lack of significantchange in diaphragm function at 10 wk occurred despite changes in serumtestosterone levels and diaphragm composition similar to those at 2.5 wk. These findings support our hypothesis that the effects oftestosterone are dependent on basal circulating androgen levels andstudy duration.