Letrozole effect in murine ventral prostate

The prostate gland is regulated by steroid hormones and complex interactions based on a subtle balance between androgen and estrogen (E2) regulate prostatic development and physiology. Interestingly, the changes in steroid hormone levels at old ages affect the hormonal milieu and contribute to the evolution of the pathological changes of the gland. We have analyzed the effects of letrozole, an aromatase inhibitor, on the structure in the ventral prostate of control and castrated adult rats. The results demonstrated alterations in prostate physiology after letrozole treatment. Serum levels of testosterone, prostate weight and proliferative index in luminal and basal cells were increased. Estrogen serum levels were not altered dramatically, in contrast to slight increase in gonadotrophin hormones seen in the castrated animals. Castration did not alter the proliferation index of basal cells. Reorganization of tissue compartments was seen with significant increase in letrozole treated animals. A decrease in androgen receptor expression was seen 21-days after the beginning of treatment with letrozole. These results were confirmed by immunohistochemistry. These results reveal new aspects in the relationship between androgen receptor and steroid metabolism in the prostate gland, demonstrating that alteration in hormone levels during a short time period induces significant alterations in prostate homeostasis.

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Androgen receptor expression of proliferating basal and luminal cells in adult murine ventral prostate

Journal of Endocrinology ◽

10.1677/joe.0.1620341 ◽

1999 ◽

Vol 162 (3) ◽

pp. 341-350 ◽

Cited By ~ 42

Author(s):

J Mirosevich ◽

JM Bentel ◽

N Zeps ◽

SL Redmond ◽

MF D'Antuono ◽

...

Keyword(s):

Androgen Receptor ◽

Epithelial Cells ◽

Prostate Gland ◽

Receptor Expression ◽

Ventral Prostate ◽

Testosterone Enanthate ◽

Basal Cells ◽

Thymidine Labelling ◽

Testosterone Administration ◽

Luminal Cells

Maintenance of the size and differentiated function of the adult prostate is dependent on testicular androgens. In this study, simultaneous androgen receptor (AR) immunohistochemistry and [(3)H]thymidine labelling was used to characterise the proliferating epithelial cells of the murine ventral prostate. Proliferation in the adult prostate was more prevalent in the basal cell population with 1.8 AR-negative cells labelled with [(3)H]thymidine as compared with 0.7% AR-expressing luminal cells. Three weeks following castration of mice, the atrophied prostate contained rudimentary glands composed of both luminal and basal cells with the proportion of AR-expressing basal cells reduced from 50 to 25%. Administration of testosterone enanthate to castrated mice induced a recapitulation of the prostate gland that was preceded by up-regulation of AR expression in basal cells to normal adult levels (50% AR-positive cells) by 12 h following testosterone injection. Proliferation of AR-positive luminal cells peaked at 48 h (22.8%) while proliferation of AR-negative basal cells peaked at 96 h (6.1%) following testosterone administration. These results suggest that distinct populations of luminal and basal cells are resistant to castration-induced involution of the prostate but remain responsive to direct or indirect testosterone effects and recapitulate the gland following administration of testosterone.

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Androgen Receptor Expression, Proliferation Index and Aneuploidy in Tissue Explant Cultures Derived Prostate Carcinoma Cells Co-Cultivated on Membranes

European Urology ◽

10.1159/000019628 ◽

1998 ◽

Vol 33 (4) ◽

pp. 414-423 ◽

Cited By ~ 7

Author(s):

Thomas Zwergel ◽

Hacer Kakirman ◽

Volker Rohde ◽

Bernd Wullich ◽

Gerhard Unteregger

Keyword(s):

Androgen Receptor ◽

Prostate Carcinoma ◽

Carcinoma Cells ◽

Receptor Expression ◽

Androgen Receptor Expression ◽

Proliferation Index ◽

Explant Cultures

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Photoperiodic Influcence on the Morphology and the Androgen Receptor Level of the Ventral Prostate Gland and Seminal Vesicles of the Djungarian Hamster (Phodopus sungorus)

Andrologia ◽

10.1111/j.1439-0272.1988.tb00668.x ◽

2009 ◽

Vol 20 (2) ◽

pp. 105-113 ◽

Cited By ~ 7

Author(s):

J. SCHINDELMEISER ◽

G. AUMÜLLER ◽

U. ENDERLE-SCHMITT ◽

M. BERGMANN ◽

K. HOFFMANN

Keyword(s):

Androgen Receptor ◽

Prostate Gland ◽

Seminal Vesicles ◽

Ventral Prostate ◽

Phodopus Sungorus ◽

Djungarian Hamster ◽

Receptor Level

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INFLUENCE OF THE ADRENAL GLAND ON PROSTATIC ACTIVITY IN ADULT RATS

Journal of Endocrinology ◽

10.1677/joe.0.0590335 ◽

1973 ◽

Vol 59 (2) ◽

pp. 335-344 ◽

Cited By ~ 8

Author(s):

B. G. MOBBS ◽

I. E. JOHNSON ◽

J. G. CONNOLLY

Keyword(s):

Nucleic Acid ◽

Adrenal Gland ◽

Acid Content ◽

Prostate Gland ◽

Ventral Prostate ◽

Nucleic Acid Content ◽

Adult Rats ◽

Intact Control ◽

Accessory Sex Glands ◽

Target Organs

SUMMARY The weight of the accessory sex glands, and the citrate and nucleic acid content of the ventral prostate (VP) glands, were examined in animals which had been adrenalectomized 30 days previously and in intact control rats. Adrenalectomy greatly reduced the citrate content, but did not affect the nucleic acid content of the VP. It was concluded that the adrenals stimulated prostatic function rather than growth. The concentration of radioactivity in the accessory sex glands of adrenalectomized and/or castrated animals after the injection of [3H]testosterone was compared with that in sham-operated controls. Radioactivity was related to the DNA content of the VP of the four groups. It was concluded that adrenalectomy facilitated the uptake and/or retention of androgen. [3H]Corticosterone was not retained by any of the accessory sex glands of animals adrenalectomized and castrated 2 days previously. It seems unlikely that the glands should be considered 'target organs' for corticosterone in the accepted sense of the term, but it is suggested that corticosteroids may help to maintain the balance between differentiation and growth in the VP by influencing the metabolism of androgens by the prostate gland.

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Relationship of ER, PR, HER2 / neu with Other Prognostic Factors in Breast Cancer along with the Role of Androgen Receptor in Triple Negative Breast Cancer

Journal of Evolution of Medical and Dental Sciences ◽

10.14260/jemds/2021/116 ◽

2021 ◽

Vol 10 (8) ◽

pp. 536-540

Author(s):

Arshi Khan ◽

Reeni Malik ◽

Pramila Jain ◽

Deepshikha Verma ◽

Vedanti Newasker

Keyword(s):

Breast Cancer ◽

Prognostic Factors ◽

Androgen Receptor ◽

Triple Negative Breast Cancer ◽

Oestrogen Receptor ◽

Triple Negative ◽

Receptor Expression ◽

Proliferation Index ◽

Lymph Node Status ◽

Significant Information

BACKGROUND Understanding various risk factors associated with breast cancer can help in early identification & prompt treatment of patients with breast cancer. Apart from clinical parameters like age, disease presentation and menopausal status, important prognostic indicators in histopathology are size and extent of tumour, histologic type,histologic grade and lymph node status. Also, there are other factors which are not only predictive of outcome, but also direct therapies against particular molecular targets. These factors are oestrogen receptor (ER) status, progesterone receptor (PR) status, HER2 / neu status, Ki-67 proliferation index & androgen receptor (AR) status. We wanted to analyse various hormone receptors & their correlation with prognostic factors. In addition, androgen receptor expression is also studied in triple negative breast cancer cases. METHODS The study included 50 cases over a period of 18 months from January 2018 to June 2019 received in the Department of Pathology, Gandhi Medical College, Bhopal, India. These cases were subjected to histopathological & immunohistochemistry (IHC) evaluation. RESULTS Among the 50 cases studied, the most common subtype was infiltrating ductal carcinoma (NOS - no special type, 84 %). Majority of patients were ER, PR, HER2 / neu negative (48 %) and among those triple negative cases, 25 % of cases were androgen receptor positive. CONCLUSIONS Expression of the hormone receptor (ER and PR) and HER2 status may provide significant information in directing patient management. Since traditional pathological methods and IHC remain standard for guiding the use of treatment, clinicians may be challenged with equivocal results that directs towards additional testing for definitive diagnosis and, better patient outcome. The most used therapy for advanced breast cancers is based on the use of AR antagonists, such as bicalutamide and enzalutamide, first- and second-generation AR antagonists respectively. Gene signatures, bioinformatics, and other clinical trials are also beneficial for clinician in estimating the benefits expected from adjuvant chemotherapy. KEY WORDS Breast Cancer, Oestrogen Receptor, Androgen Receptor, Triple Negative

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MEASUREMENT OF FREE AND OCCUPIED CYTOPLASMIC AND NUCLEAR ANDROGEN RECEPTOR SITES IN RAT VENTRAL PROSTATE GLAND

Journal of Endocrinology ◽

10.1677/joe.0.0740393 ◽

1977 ◽

Vol 74 (3) ◽

pp. 393-404 ◽

Cited By ~ 41

Author(s):

PETER DAVIES ◽

PHILIP THOMAS ◽

KEITH GRIFFITHS

Keyword(s):

Androgen Receptor ◽

Specific Binding ◽

Prostate Gland ◽

Ventral Prostate ◽

Reliable Estimate ◽

Exchange Method ◽

Receptor Proteins ◽

Receptor Sites ◽

Rat Ventral Prostate ◽

Fold Excess

SUMMARY A method has been developed which allows the estimation of occupied and unoccupied androgen receptor sites in both cytoplasmic and nuclear fractions of rat ventral prostate. The procedure involves precipitation of receptor proteins and incubation of precipitates with labelled 5α-dihydrotestosterone. Uptake of 3H-labelled steroid at 0–4 °C gives an indication of free receptor, whereas binding at a raised temperature (15 °C) allows estimation of occupied receptor. Non-specific binding was measured in the presence of a 100-fold excess of unlabelled 5α-dihydrotestosterone. The exchange method was specific for androgens, and specific binding was detected only in fractions of androgen-dependent tissues. The method can be applied to cytosol, whole nuclei, chromatin and salt-extractable and salt-resistant protein preparations from nuclear fractions, and gives a reliable estimate of total receptor sites when occupied as compared with control measurements of unoccupied sites.

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ICI 176,334: A NOVEL NON–STEROIDAL, PERIPHERALLY SELECTIVE ANTIANDROGEN

Journal of Endocrinology ◽

10.1677/joe.0.113r007 ◽

1987 ◽

Vol 113 (3) ◽

pp. R7-R9 ◽

Cited By ~ 104

Author(s):

B.J.A. Furr ◽

B. Valcaccia ◽

B. Curry ◽

J.R. Woodburn ◽

G. Chesterson ◽

...

Keyword(s):

Testosterone Propionate ◽

Prostate Gland ◽

Ventral Prostate ◽

Adult Rats ◽

Androgen Action ◽

Serum Lh ◽

Accessory Sex Organs ◽

Hypothalamic Pituitary Axis ◽

Rat Prostate ◽

Higher Doses

ABSTRACT Pure antiandrogens, like flutamide, antagonize androgen action both peripherally and centrally at the hypothalamic–pituitary axis, which leads to an increase in LH and testosterone secretion. A new non–steroidal antiandrogen ICI 176,334 ((2RS)4′-cyano-3-(4-fluorophenylsulphonyl)-2-hydroxy-2-methyl-3′-trifluoromethyl)propion-anilide) has now been discovered which causes regression of the accessory sex organs but does not increase serum concentrations of LH and androgens. ICI 176,334 binds to rat prostate androgen receptors with an affinity around fourfold that of hydroxyflutamide. When administered s.c. concurrently with testosterone propionate (200μg/kg) for 7 days to immature castrated rats, ICI 176,334 (10mg/kg) significantly (P<0.001) inhibited growth of the seminal vesicles and ventral prostate gland. Oral administration of ICI 176,334 at doses of 1, 5 and 25mg/kg for 14 days to adult rats caused a dose–related reduction in accessory sex organ weights but had no effect on the testes. None of these doses caused a significant increase in serum LH and testosterone. Flutamide was around fourfold less potent and significantly increased serum LH and testosterone at the higher doses. ICI 176,334 was well tolerated. ICI 176,334 should, therefore, prove useful for the treatment of androgen–responsive benign and malignant diseases.

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Bisphenol A Modifies the Regulation Exerted by Testosterone on 5α-Reductase Isozymes in Ventral Prostate of Adult Rats

BioMed Research International ◽

10.1155/2013/629235 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Pilar Sánchez ◽

Beatriz Castro ◽

Jesús M. Torres ◽

Asunción Olmo ◽

Raimundo G. del Moral ◽

...

Keyword(s):

Bisphenol A ◽

Prostate Gland ◽

Ventral Prostate ◽

Mrna Levels ◽

Dependent Manner ◽

Adult Rats ◽

Short Term Exposure ◽

Rat Prostate ◽

And Function ◽

Dose Dependent

The development, growth, and function of the prostate gland depend on androgen stimulation. The primary androgen in prostate is 5α-dihydrotestosterone (DHT) which is synthesized from circulating testosterone (T) through the action of 5α-reductase (5α-R). Although 5α-R occurs as five isozymes, only 5α-R1 and 5α-R2 are physiologically involved in steroidogenesis. The endocrine disruptor bisphenol A (BPA) alters sexual organs, including the prostate. Our previous findings indicated that BPA decreased the expression of 5α-R1 and 5α-R2 in rat prostate but also circulating T. Thus, it is unclear whether BPA exerts this effect on 5α-R isozymes by reducing circulating T or by any other mechanism. In this study, we examine the effects of short-term exposure to BPA at doses below 25 μg/Kg/d and above 300 μg/Kg/d of the TDI on mRNA levels of 5α-R1 and 5α-R2 in prostate of adult castrated rats supplemented with T to achieve constant circulating T levels. mRNA levels were measured by absolute quantitative RT-PCR, T levels by RIA, and DHT levels by ELISA. Our results indicated that in castrated rats treated with T BPA at the two doses studied significantly decreased the mRNA levels of both 5α-R isozymes in a dose-dependent manner without modifications in circulating T.

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