Sex-steroid receptors in the diethylnitrosamine model of hepatocarcinogenesis: modifications by gonadal ablation and steroid replacement therapy

ABSTRACT The results of this study confirm our previous report of increased androgen receptor expression in livers of female SUAH Wistar rats during development of liver tumours induced by diethylnitrosamine (DENA). In adult female rats not treated with DENA, removal of the ovary increased liver androgen receptor levels but testosterone did not further enhance the androgen receptor status of ovariectomized rats. In normal adult males the testis and/or testosterone maintained high levels of androgen receptors but oestrogen reduced them in castrated rats. Oestrogen receptor levels were not significantly changed in either males or females by gonadectomy. Treatment of female rats with DENA for 10 and 16 weeks increased liver androgen receptors but oestrogen receptors were only reduced by 16 weeks of DENA treatment, whether the rats were intact or ovariectomized. Concentrations of liver androgen receptors were increased in intact and castrated male rats by 10 and 16 weeks of DENA treatment, an increase not seen in the previous experiments. Oestrogen appeared to inhibit both the increases in liver androgen receptor expression and liver tumour development in rats treated with the weakly carcinogenic dose of 10 weeks of DENA. However, the full carcinogenic dose of 16 weeks of DENA increased liver androgen receptors and decreased oestrogen receptors in female rats regardless of sex-steroid status. Development of malignant hepatocellular carcinoma (HCC) was associated with both an increase in liver androgen receptors and a decrease in oestrogen receptors. Maintenance of relatively high levels of liver oestrogen receptors appeared to protect the liver against development of HCC.

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Increased hepatic androgen receptor expression in female rats during diethylnitrosamine liver carcinogenesis

Gastroenterology ◽

10.1016/0016-5085(88)90012-1 ◽

1988 ◽

Vol 94 (5) ◽

pp. 1193-1200 ◽

Cited By ~ 21

Author(s):

J.L. Ostrowski ◽

P.M. Ingleton ◽

J.C.E. Underwood ◽

M.A. Parsons

Keyword(s):

Androgen Receptor ◽

Receptor Expression ◽

Androgen Receptor Expression ◽

Female Rats ◽

Liver Carcinogenesis

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Effects of Aluminum Exposure on Serum Sex Hormones and Androgen Receptor Expression in Male Rats

Biological Trace Element Research ◽

10.1007/s12011-011-9098-6 ◽

2011 ◽

Vol 144 (1-3) ◽

pp. 1050-1058 ◽

Cited By ~ 23

Author(s):

Hao Sun ◽

Chongwei Hu ◽

Linlin Jia ◽

Yanzhu Zhu ◽

Hansong Zhao ◽

...

Keyword(s):

Androgen Receptor ◽

Sex Hormones ◽

Receptor Expression ◽

Androgen Receptor Expression ◽

Male Rats ◽

Aluminum Exposure

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Expression level of androgen receptors in tumor tissue and its prognostic significance in primary operable luminal breast cancer without overexpression of Her2/neu in postmenopausal women

Kazan medical journal ◽

10.17816/kmj2019-112 ◽

2019 ◽

Vol 100 (1) ◽

pp. 112-116 ◽

Cited By ~ 1

Author(s):

O I Kit ◽

Yu S Shatova ◽

V V Tokmakov ◽

I A Novikova ◽

E P Ul’yanova ◽

...

Keyword(s):

Breast Cancer ◽

Androgen Receptor ◽

Postmenopausal Women ◽

Androgen Receptors ◽

Prognostic Significance ◽

Receptor Expression ◽

Androgen Receptor Expression ◽

Luminal Breast Cancer ◽

Luminal A ◽

Luminal B

Aim. To evaluate the expression level and prognostic significance of androgen in primary operable luminal breast cancer without overexpression of Her2/neu in postmenopausal women. Methods. We analyzed treatment outcomes of 60 cases of primary operable (T1-2N0M0) luminal breast cancer without overexpression of Her2/neu in postmenopausal women. The follow-up period was 5 years. All cases were divided by immunohistochemical method into luminal A (20 females) and luminal B (40 patients) subtypes. Along with the standard panel of immunohistochemical markers, expression of nuclear androgen receptors was measured in tumor tissues of all patients. Depending on the expression levels, patients with luminal A and B subtypes were divided into three groups: (1) with high, (2) moderate and (3) low or negative expression. Results. Mean levels of androgen receptor expression in the nuclei of tumor cells in patients with luminal A subtype (57.3±5.9%) were higher than those of luminal B subtype (21.4±4.04%) by 62.7% (Mann-Whitney test, р=0.0026). In patients with luminal A subtype, the maximal accumulation of androgen receptors in the nuclei of tumor cells was 2.7 times higher (р=0.0023) than in patients with luminal B subtype. All cases diagnosed with the disease progression were characterized by low or negative level of nuclear androgen receptor expression. Conclusion. Negative and low levels of androgen receptor expression in tumor tissues of postmenopausal patients with luminal primary operable breast cancer without overexpression of Her2/neu might be an independent factor associated with poor prognosis.

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Stereological analysis of androgen receptors in prostate cancer and benign prostatic hyperplasia

Medicinski pregled ◽

10.2298/mpns1804089t ◽

2018 ◽

Vol 71 (3-4) ◽

pp. 89-95

Author(s):

Sandra Trivunic-Dajko ◽

Jovo Bogdanovic ◽

Sasa Vojinov ◽

Andrejic Visnjic

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Benign Prostatic Hyperplasia ◽

Prostatic Cancer ◽

Androgen Receptors ◽

Immunohistochemical Analysis ◽

Prostatic Hyperplasia ◽

Receptor Expression ◽

Androgen Receptor Expression ◽

Stereological Analysis

Introduction. Through androgen receptors, androgens regulate prostate cellular growth and function, proliferation, differentiation, apoptosis, lipid metabolism and secretory activity, as well as development and progression of prostate cancer. Prostate cancer, and its primary glandular tissue are influenced by hormones, and it is used for therapeutic purposes. Anti-androgen treatment is carried out in patients with metastatic prostatic cancer, in order to block effects of androgens. Immunohistochemical analysis of androgen receptors in the prostate cancer tissue may help us to assume how the tumors will react to the anti-androgen therapy, if they are androgen-positive, -negative, or hormone resistant tumors. Knowledge of the presence of androgen receptors in the tumor tissue may be a prognostic indicator in histopathological analysis. The aim of this study was stereological evaluation of androgen receptor expression in patients with benign prostatic hyperplasia and in patients with prostatic cancer, before therapy. Material and Methods. Immunohistochemical analysis was carried out using anti-human androgen receptor monoclonal antibody 441. The presence and intensity of the androgen receptors were evaluated in 195 patients: 165 with benign prostatic hyperplasia and 30 with prostatic cancer using Weibel?s multi-purpose M 42 stereological test system. Material was obtained by needle biopsy or transurethral resection of the prostate. Results. All secretory cells in patients with benign prostatic hyperplasia were androgen positive, while in patients with prostatic cancer, all tumors were mostly androgen positive, some with foci of negativity. The resulting negative correlation with Gleason score and International Society of Urological Pathology grade was not statistically significant. Conclusion. Study results of stereological analysis of androgen receptors indicate that prior the therapy prostate cancer is androgendependent, with a high level of androgen receptor expression, although slightly lower compared to benign prostatic hyperplasia.

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Colonic transit in rats: effect of ovariectomy, sex steroid hormones, and pregnancy

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1986.251.1.g46 ◽

1986 ◽

Vol 251 (1) ◽

pp. G46-G50 ◽

Cited By ~ 14

Author(s):

J. P. Ryan ◽

A. Bhojwani

Keyword(s):

Steroid Hormones ◽

Colonic Transit ◽

Sex Steroid Hormones ◽

Female Rats ◽

Male Rats ◽

Ovariectomized Rats ◽

Sex Steroid ◽

Mechanical Activity ◽

Geometric Center

In vitro studies suggest that the female sex steroid hormones [estrogen (E) and progesterone (P)] can affect the myoelectric and mechanical activity of colonic smooth muscle. The present study was designed to examine the influence of the hormones on colonic transit in vivo. Transit was assessed by quantifying the distribution within the colon of a radiolabeled marker (0.5 microCi Na251CrO4), using the geometric center method of analysis. Studies were performed with adult male rats and the following groups of female rats: nonpregnant, ovariectomized, ovariectomy plus hormone pretreatment (100 micrograms X kg-1 X day-1 E + 2.5 mg X kg-1 X day-1 P for 4 days), and pregnant (day 18). Hormone-pretreated animals were studied 24 h following the fourth injection. The data can be summarized as follows. 1) Colonic transit was affected by the timing of the estrus cycle. Rats determined to be in proestrus-estrus had a geometric center value (1.97 +/- 0.50) significantly less than that of metestrus-diestrus animals (4.25 +/- 0.57). 2) Ovariectomy eliminated the biphasic transit pattern observed in estrus-cycling females and resulted in a geometric center value (4.19 +/- 0.17) comparable with that of the metestrus-diestrus animals. 3) E + P pretreatment of ovariectomized rats resulted in a significant decrease in the geometric center (1.94 +/- 0.19) compared with the untreated ovariectomized rats. 4) The geometric center value in pregnant animals (2.22 +/- 0.20) closely resembled the transit data for proestrus-estrus animals and hormone-pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

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