Effects of androgen and ageing on gene expression of vasoactive intestinal polypeptide in rat corpus cavernosum

Zhang, Shen; Lu, Yingli; Chen, Z.D.; Chen, F.; Chen, Z.

doi:10.1046/j.1464-410x.2000.00721.x

Cited by 19 publications

(13 citation statements)

References 27 publications

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“…Andersen et al (2002) reported that free testosterone levels in Wistar rats decreased from 3 to 22 months in Wistar rats, but no intermediate ages were studied. Shen et al (2000) found that free testosterone concentrations were similar in Sprague-Dawley rats at 2- and 13-months of age, similar to our current results. Thus, future studies would help to resolve some differences in results.…”

Section: Discussionsupporting

confidence: 91%

Changes in androgen receptor, estrogen receptor alpha, and sexual behavior with aging and testosterone in male rats

Gore

2010

Hormones and Behavior

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Reproductive aging in males is characterized by a diminution in sexual behavior beginning in middle age. We investigated the relationships among testosterone, androgen receptor (AR) and estrogen receptor alpha (ERα) cell numbers in the hypothalamus, and their relationship to sexual performance in male rats. Young (3 months) and middle-aged (12 months) rats were given sexual behavior tests, then castrated and implanted with vehicle or testosterone capsules. Rats were tested again for sexual behavior. Numbers of AR and ERα immunoreactive cells were counted in the anteroventral periventricular nucleus and the medial preoptic nucleus, and serum hormones were measured. Middle-aged intact rats had significant impairments of all sexual behavior measures compared to young males. After castration and testosterone implantation, sexual behaviors in middle-aged males were largely comparable to those in the young males. In the hypothalamus, AR cell density was significantly (5-fold) higher, and ERα cell density significantly (6-fold) lower, in testosterone- than vehicle-treated males, with no age differences. Thus, restoration of serum testosterone to comparable levels in young and middle-aged rats resulted in similar preoptic AR and ERα cell density concomitant with a reinstatement of most behaviors. These data suggest that age-related differences in sexual behavior cannot be due to absolute levels of testosterone, and further, the middle-aged brain retains the capacity to respond to exogenous testosterone with changes in hypothalamic AR and ERα expression. Our finding that testosterone replacement in aging males has profound effects on hypothalamic receptors and behavior has potential medical implications for the treatment of age-related hypogonadism in men.

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Section: Discussionsupporting

confidence: 91%

Changes in androgen receptor, estrogen receptor alpha, and sexual behavior with aging and testosterone in male rats

Gore

2010

Hormones and Behavior

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“…The T and DHT levels in castrated rats and the DHT level in finasteride‐treated groups were significantly lower than those in the control group. In the castrated animals, there was a high degree of fibrosis in the corpus cavernosum with irregularly arranged collagenous fibers and a marked decrease in smooth muscle fibers, while in the DHT‐inhibited group (finasteride‐treated), the corpus cavernosum comprised a substantial amount of thick and irregularly arranged collagenous fibers, but the degree of fibrosis was less than that of the castration group (Shen et al, 2000). This work suggests that because finasteride inhibits the action of DHT but not T on the corporal cavernosal tissue, the degree of fibrosis was less in the DHT‐inhibited group than in the castration group.…”

Section: Deficiency In 5 α‐Reductasementioning

confidence: 90%

The Effect of 5 α‐Reductase Inhibitors on Erectile Function

Cangüven

Burnett

2008

Journal of Andrology

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The 5 a-reductase inhibitors, which inhibit conversion of testosterone to dihydrotestosterone, are used for miscellaneous clinical applications, including the treatment of benign prostatic hyperplasia and male pattern hair loss, and for possible reduction of the risk of prostate cancer. Erectile dysfunction has been associated with 5 a-reductase inhibitors. Overall, reports in the literature suggest rates of erectile dysfunction to be between 0.8%-33% in men using these medications. However, randomized controlled studies report the rates of erectile dysfunction to be between 0.8%-15.8%. The possible risk association is that these medications impact androgen function, which is understood to contribute to normal erectile physiology. The 5 a-reductase inhibitors result in a drop in median serum dihydrotestosterone levels by 60%-93% within 2 years, but there is no major change in testosterone levels. In this review, we surveyed studies on erectile dysfunction in patients treated with 5 areductase inhibitors and critically examined the evidence that associates 5 a-reductase inhibitors and erectile dysfunction. We conclude that 5 a-reductase inhibitors do not lead to erectile dysfunction to a significant degree, and we support the position that dihydrotestosterone is less relevant than testosterone in erectile function.J Androl 2008;29:514-523T he 5 a-reductase inhibitors (5ARIs) have been successfully used for more than 20 years for treatments of benign prostatic hyperplasia (BPH) and male pattern hair loss, and lately they have been evaluated for reduction in prostate cancer risk. Presently available orally administered 5ARIs, finasteride and dutasteride, inhibit 5 a-reductase, an enzyme that catalyzes the irreversible reduction of testosterone (T) to dihydrotestosterone (DHT), with NADPH as the hydrogen donor (Russell and Wilson, 1994). There are 2 isoenzyme forms (types I and II). Type I is located predominantly in the skin, in both hair follicles and sebaceous glands, as well as in the liver, prostate, and kidney and is responsible for approximately one-third of circulating DHT (Thiboutot et al, 1995). Type II is found in the prostate, seminal vesicles, epididymis, hair follicles, and liver, and is responsible for the remaining two-thirds of circulating DHT (Thigpen et al, 1993a;Gisleskog et al, 1998). Finasteride inhibits type II, while dutasteride is an inhibitor of both types and may decrease circulating DHT to a greater extent than finasteride (Clark et al, 2004).The sex steroidal influence in the physiology of the erectile response has been an issue of controversy for many years. Points of view have ranged from thought that the androgens offer an unneeded role in physiological mechanisms of penile erection (Handelsman and Zajac, 2004) to the view that these hormones critically influence structural and functional circumstances required for the erectile response (Gooren and Saad, 2006;Traish and Guay, 2006).We are able to treat patients for prostatic or hair diseases by decreasing their DHT levels. D...

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“…The test tubes were sealed and placed in a water bath (80°C) for 2 h. After that, the samples were cooled to room temperature, and 5 ml of potassium carbonate solution (7%) was added to the reaction mixture. The mixture was then Serum concentrations of E2, DHT, aminotransferase, and serum static lipid profi le Serum E2 and DHT were measured as described in previous studies ( 28,29 ). Serum lipid parameters were measured with a lipidmeasuring kit (Wako Pure Chemical Industries Ltd, Osaka, Japan) according to the protocol provided with kit.…”

Section: Measurement Of Static Levels Of Fatty Acids From Liver Usingmentioning

confidence: 99%

Differential effects of estrogen/androgen on the prevention of nonalcoholic fatty liver disease in the male rat

Zhang

Liu

Wang

et al. 2013

Journal of Lipid Research

128

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Nonalcoholic fatty liver disease (NAFLD) is strongly linked to central obesity, insulin resistance (IR), and metabolic syndrome ( 1 ), and its increasing prevalence is estimated at 20-30% among the adult population in industrialized countries ( 2 ).Although estrogen and androgen are important regulators of lipid homeostasis ( 3, 4 ), data on their possible infl uence on the prevention or treatment of NAFLD are scarce. Clinically, tamoxifen (Tam) is widely used for the treatment of estrogen-responsive breast cancer, but its frequent side effect is the development of NAFLD. Forty-three percent of patients with Tam-treated breast cancer develop steatosis Abstract It is important to clarify the distinct contributions of estrogen/estrogen receptor (ER) and androgen/androgen receptor (AR) signaling and their reciprocal effects on the regulation of hepatic lipid homeostasis. We studied the molecular mechanisms underlying the preventive effects of estradiol (E2), dihydrotestosterone (DHT), or E2+DHT on high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) in an orchidectomized Sprague-Dawley (SD) rat model. E2 is shown to be associated with decreased fatty acid synthesis in hepatic zone 3-specifi c manner by increasing the phosphorylation of acetyl coenzyme-A carboxylase via an ER ␣ -mediated pathway. DHT is shown to be associated with decreased lipid accumulation and cholesterol synthesis in a hepatic zone 1-specifi c manner by increasing expression of carnitine palmitotyltransferase1 and phosphorylation of 3-hydroxy-3-methyl-glutaryl-CoA reductase via an AR-mediated pathway. E2+DHT showed an additive positive effect and normalized all three impaired zones of the liver. Gene expression changes in human severe liver steatosis were similar to those of experimental rat NAFLD. Steroids reversed the histopathological NAFLD changes, likely by decreasing fatty acid and cholesterol synthesis and increasing ␤ -oxidation. The diverse steroid effects (ER/AR) on NAFLD prevention in male rats indicate the potential applicability of ER/AR modulators for NAFLD treatment. -

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Effects of androgen and ageing on gene expression of vasoactive intestinal polypeptide in rat corpus cavernosum

Cited by 19 publications

References 27 publications

Changes in androgen receptor, estrogen receptor alpha, and sexual behavior with aging and testosterone in male rats

Changes in androgen receptor, estrogen receptor alpha, and sexual behavior with aging and testosterone in male rats

The Effect of 5 α‐Reductase Inhibitors on Erectile Function

Differential effects of estrogen/androgen on the prevention of nonalcoholic fatty liver disease in the male rat

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