Hormonal steroid receptors in intracranial tumours and their relevance in hormone therapy

Twenty-eight patients with metastatic renal cell carcinoma entered a multicentric prospective study to evaluate the response to high-dose medroxyprogesterone acetate (MPA) and testosterone in MPA failures in relation to sex steroid receptors. No objective remission was seen in the 24 evaluable patients, and only disease stabilizations of short duration were achieved in one-third of treated patients. Stabilizations achieved with second line testosterone were all seen in patients unresponsive to MPA. Receptor studies demonstrated that estrogen, progesterone, or androgen receptors were found in low concentrations and in only 6 of 23 tumors (26%) and 13 normal tissue samples (56%). Surprisingly, no disease stabilization was achieved in patients positive for receptors. It can be concluded that the occasional objective responses to hormone therapy reported in the literature may have been due to some cytotoxic effect of hormone therapy rather than to a true hormonal mechanism.

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Hormone therapy and breast cancer: emerging steroid receptor mechanisms

Journal of Molecular Endocrinology ◽

10.1530/jme-18-0094 ◽

2018 ◽

Vol 61 (4) ◽

pp. R133-R160 ◽

Cited By ~ 5

Author(s):

Meghan S Perkins ◽

Renate Louw-du Toit ◽

Donita Africander

Keyword(s):

Breast Cancer ◽

Side Effects ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Hormone Therapy ◽

Cancer Biology ◽

Steroid Receptors ◽

Current Knowledge ◽

Steroid Receptor ◽

Cancer Pathogenesis

Although hormone therapy is widely used by millions of women to relieve symptoms of menopause, it has been associated with several side effects such as coronary heart disease, stroke and increased invasive breast cancer risk. These side effects have caused many women to seek alternatives to conventional hormone therapy, including the controversial custom-compounded bioidentical hormone therapy suggested to not increase breast cancer risk. Historically, estrogens and the estrogen receptor were considered the principal factors promoting breast cancer development and progression; however, a role for other members of the steroid receptor family in breast cancer pathogenesis is now evident, with emerging studies revealing an interplay between some steroid receptors. In this review, we discuss examples of hormone therapy used for the relief of menopausal symptoms, highlighting the distinction between conventional hormone therapy and custom-compounded bioidentical hormone therapy. Moreover, we highlight the fact that not all hormones have been evaluated for an association with increased breast cancer risk. We also summarize the current knowledge regarding the role of steroid receptors in mediating the carcinogenic effects of hormones used in menopausal hormone therapy, with special emphasis on the influence of the interplay or crosstalk between steroid receptors. Unraveling the intertwined nature of steroid hormone receptor signaling pathways in breast cancer biology is of utmost importance, considering that breast cancer is the most prevalent cancer among women worldwide. Moreover, understanding these mechanisms may reveal novel prevention or treatment options and lead to the development of new hormone therapies that do not cause increased breast cancer risk.

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Danoval and omnadren effect on the patients with dysfunctional uterine bleedings during the premenopause

Journal of obstetrics and women s diseases ◽

10.17816/jowd87965 ◽

1999 ◽

Vol 48 (1) ◽

pp. 20-24

Author(s):

E. G. Gumenyuk ◽

L. A. Samorodinova

Keyword(s):

Hormone Therapy ◽

Steroid Hormones ◽

Initial Level ◽

Steroid Receptors ◽

Wide Spectrum ◽

Receptor Apparatus ◽

Level Reduction

Initial level of gonadothropic, steroid hormones in the blood, receptors of estradiol and progesteron of the endometrium in the patients with dysfunctional uterine bleedings during the premenopause, and their dunamics during and after hormone therapy were studied. Danoval and oxy prog esterone-capronat in combination with omnadren had different effect on the parameters of the hormonal homeostasis and receptor apparatus of the endometrium. Antigonadоthropic effect of danoval results in FSG level reduction, estradiol and progesterone decrease in the blood and that of steroid receptors in the endometrium, that did not take place with other therapies. The effectiveness of the treatment with danoval was 88,24%, and it was 62,50% when oxy prog esterone-capronat with omnadren therapy was used. It is concluded that danoval prescription to the patients with dysfunctional uterine bleedings during the menopause is more expedient for the wide spectrum of antigonadothropic effect.

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Role of molecular chaperones in steroid receptor action

Essays in Biochemistry ◽

10.1042/bse0400041 ◽

2004 ◽

Vol 40 ◽

pp. 41-58 ◽

Cited By ~ 149

Author(s):

William B Pratt ◽

Mario D Galigniana ◽

Yoshihiro Morishima ◽

Patrick J M Murphy

Keyword(s):

Transcriptional Activation ◽

Protein Trafficking ◽

Steroid Receptors ◽

Transcriptional Regulatory ◽

Ubiquitin Proteasome ◽

Proteasome Pathway ◽

Receptor Action ◽

Binding Cleft ◽

Hsp 90

Unliganded steroid receptors are assembled into heterocomplexes with heat-shock protein (hsp) 90 by a multiprotein chaperone machinery. In addition to binding the receptors at the chaperone site, hsp90 binds cofactors at other sites that are part of the assembly machinery, as well as immunophilins that connect the assembled receptor-hsp90 heterocomplexes to a protein trafficking pathway. The hsp90-/hsp70-based chaperone machinery interacts with the unliganded glucocorticoid receptor to open the steroid-binding cleft to access by a steroid, and the machinery interacts in very dynamic fashion with the liganded, transformed receptor to facilitate its translocation along microtubular highways to the nucleus. In the nucleus, the chaperone machinery interacts with the receptor in transcriptional regulatory complexes after hormone dissociation to release the receptor and terminate transcriptional activation. By forming heterocomplexes with hsp90, the chaperone machinery stabilizes the receptor to degradation by the ubiquitin-proteasome pathway of proteolysis.

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