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Fulltext Linking Ayurveda and Western medicine by integrative analysis

Fauzi FM, Koutsoukas A, Lowe R, Joshi K, Fan TP, Glen RC, et al.

J Ayurveda Integr Med, 2013 Apr;4(2):117-9.
PMID: 23930045 DOI: 10.4103/0975-9476.113882

In this article, we discuss our recent work in elucidating the mode-of-action of compounds used in traditional medicine including Ayurvedic medicine. Using computational ('in silico') approach, we predict potential targets for Ayurvedic anti-cancer compounds, obtained from the Indian Plant Anticancer Database given its chemical structure. In our analysis, we observed that: (i) the targets predicted can be connected to cancer pathogenesis i.e. steroid-5-alpha reductase 1 and 2 and estrogen receptor-β, and (ii) predominantly hormone-dependent cancer targets were predicted for the anti-cancer compounds. Through the use of our in silico target prediction, we conclude that understanding how traditional medicine such as Ayurveda work through linking with the 'western' understanding of chemistry and protein targets can be a fruitful avenue in addition to bridging the gap between the two different schools of thinking. Given that compounds used in Ayurveda have been tested and used for thousands of years (although not in the same approach as Western medicine), they can potentially be developed into potential new drugs. Hence, to further advance the case of Ayurvedic medicine, we put forward some suggestions namely: (a) employing and integrating novel analytical methods given the advancements of 'omics' and (b) sharing experimental data and clinical results on studies done on Ayurvedic compounds in an easy and accessible way.

Matched MeSH terms: Estrogen Receptor beta
Fulltext Role of co-expression of estrogen receptor beta and Ki67 in prostate adenocarcinoma

Azizan N, Hayati F, Tizen NMS, Farouk WI, Masir N

Investig Clin Urol, 2018 07;59(4):232-237.
PMID: 29984337 DOI: 10.4111/icu.2018.59.4.232

Purpose: To evaluate the expression of estrogen receptor (ER)-beta and Ki67 in prostate cancer and study their relationship.
Materials and Methods: We analyzed 101 cases of prostate adenocarcinoma diagnosed from January 2011 to June 2015 in 100 patients. Immunohistochemical staining of ER-beta and Ki67 was analyzed according to Gleason score categorized into prognostic groups of 1 to 5. Double-immunofluorescent staining of ER-beta and Ki67 was performed in a total of 20 cases to study the co-expression and the relationship between these markers within the same tumor.
Results: A total of 53 of 101 cases (52.5%) were positive for ER-beta expression. There was a positive correlation whereby a high percentage of ER-beta expression was seen in the higher prognostic groups (groups 4 and 5; p=0.007). High Ki67 expression was observed in the higher prognostic group, whereas low Ki67 or negative expression was found in the lower prognostic group (p<0.001). The majority of cases evaluated with double-immunofluorescent staining (14/20) showed co-expression of ER-beta and Ki67 at the individual cell level.
Conclusions: ER-beta and Ki67 are independent tumor markers in high prognostic groups. Hence, co-expression of ER-beta and Ki67 indicates a more aggressive tumor with a poorer prognosis.

Matched MeSH terms: Estrogen Receptor beta/metabolism*
Fulltext Phytoestrogens by inhibiting the non-classical oestrogen receptor, overcome the adverse effect of bisphenol A on hFOB 1.19 cells

Thent ZC, Froemming GRA, Ismail ABM, Fuad SBSA, Muid S

Iran J Basic Med Sci, 2020 Sep;23(9):1155-1163.
PMID: 32963737 DOI: 10.22038/ijbms.2020.45296.10545

Objectives: Since bisphenol A (BPA) induces bone loss and phytoestrogens enhance the osteoblastogenesis by binding to the non-classical and classical oestrogen receptors, respectively, the present study was aimed to observe the osteoprotective effect of phytoestrogens on BPA-induced osteoblasts in hFOB 1.19 cells.
Materials and Methods: All groups of hFOB 1.19 cells were induced with 12.5 μg/ml of BPA except the control (Ctrl) group. Meanwhile, treated groups received phytoestrogens; Daidzein (Dz), Genistein (Gt), Equol (Eq) and 17β-oestradiol (Est) in different concentrations for 24 hr duration.
Results: We found that the protein expression of non-classical oestrogen-related receptor (ERRG) was highly expressed in BPA group, whereas classical oestrogen receptor alpha (ERα) and oestrogen receptor beta (ERβ) were relatively increased with phytoestrogens treatment under BPA exposure. The dense actin cytoskeletal filaments were also observed. qRT-PCR showed up-regulation of mitogen-activated protein kinase 3 (MAPK3) and G protein-coupled receptor 30 (GPR30) expressions; significant down-regulation of ERRG and up-regulation of ERα and ERβ were observed in phytoestrogens-treated cells, which was supported by the increased expressions of oestrogen receptor 1 (ESR1) and oestrogen receptor 2 (ESR2).
Conclusion: Phytoestrogens improved the deteriorative effect of BPA via down-regulation of ERRG in hFOB 1.19 cells. This study showed that the efficacy of consumption of phytoestrogens in rendering them as potential therapeutic strategy in combating the adverse bone effects of BPA.

Matched MeSH terms: Estrogen Receptor beta
Fulltext Tocotrienols and breast cancer: the evidence to date

Nesaretnam K, Meganathan P, Veerasenan SD, Selvaduray KR

Genes Nutr, 2012 Jan;7(1):3-9.
PMID: 21516480 DOI: 10.1007/s12263-011-0224-z

Breast cancer is the second most frequent cancer affecting women worldwide after lung cancer. The toxicity factor associated with synthetic drugs has turned the attention toward natural compounds as the primary focus of interest as anticancer agents. Vitamin E derivatives consisting of the well-established tocopherols and their analogs namely tocotrienols have been extensively studied due to their remarkable biological properties. While tocopherols have failed to offer protection, tocotrienols, in particular, α-, δ-, and γ-tocotrienols alone and in combination have demonstrated anticancer properties. The discovery of the antiangiogenic, antiproliferative, and apoptotic effects of tocotrienols, as well as their role as an inducer of immunological functions, not only reveals a new horizon as a potent antitumor agent but also reinforces the notion that tocotrienols are indeed more than antioxidants. On the basis of a transcriptomic platform, we have recently demonstrated a novel mechanism for tocotrienol activity that involves estrogen receptor (ER) signaling. In silico simulations and in vitro binding analyses indicate a high affinity of specific forms of tocotrienols for ERβ, but not for ERα. Moreover, we have demonstrated that specific tocotrienols increase ERβ translocation into the nucleus which, in turn, activates the expression of estrogen-responsive genes (MIC-1, EGR-1 and Cathepsin D) in breast cancer cells only expressing ERβ cells (MDA-MB-231) and in cells expressing both ER isoforms (MCF-7). The binding of specific tocotrienol forms to ERβ is associated with the alteration of cell morphology, caspase-3 activation, DNA fragmentation, and apoptosis. Furthermore, a recently concluded clinical trial seems to suggest that tocotrienols in combination with tamoxifen may have the potential to extend breast cancer-specific survival.

Matched MeSH terms: Estrogen Receptor beta
Fulltext Tualang Honey Protects against BPA-Induced Morphological Abnormalities and Disruption of ERα, ERβ, and C3 mRNA and Protein Expressions in the Uterus of Rats

Mohamad Zaid SS, Kassim NM, Othman S

Evid Based Complement Alternat Med, 2015;2015:202874.
PMID: 26788107 DOI: 10.1155/2015/202874

Bisphenol A (BPA) is an endocrine disrupting chemical (EDC) that can disrupt the normal functions of the reproductive system. The objective of the study is to investigate the potential protective effects of Tualang honey against BPA-induced uterine toxicity in pubertal rats. The rats were administered with BPA by oral gavage over a period of six weeks. Uterine toxicity in BPA-exposed rats was determined by the degree of the morphological abnormalities, increased lipid peroxidation, and dysregulated expression and distribution of ERα, ERβ, and C3 as compared to the control rats. Concurrent treatment of rats with BPA and Tualang honey significantly improved the uterine morphological abnormalities, reduced lipid peroxidation, and normalized ERα, ERβ, and C3 expressions and distribution. There were no abnormal changes observed in rats treated with Tualang honey alone, comparable with the control rats. In conclusion, Tualang honey has potential roles in protecting the uterus from BPA-induced toxicity, possibly accounted for by its phytochemical properties.

Matched MeSH terms: Estrogen Receptor beta
Estrogenic phytochemical from Labisia pumila (Myrsinaceae) with selectivity towards estrogen receptor alpha and beta subtypes

Muhamad M, Choo CY, Hasuda T, Hitotsuyanagi Y

Fitoterapia, 2019 Sep;137:104256.
PMID: 31295513 DOI: 10.1016/j.fitote.2019.104256

Labisia pumila var. alata (Myrsinaceae) or "Kacip fatimah" is a famous Malay traditional herb used for the maintenance of women's health. The extracts of L.pumila displayed estrogenic activity in rats. Nonetheless, the estrogenic bioactives were not identified. The aim of the study is to identify estrogenic compounds contributing to the established estrogenic activity. Bioactivity-guided-isolation method guided the isolation of pure bioactives. The hexane extract was subjected to a series of silica gel flash and open column chromatography with increasing amount of ethyl acetate in hexane or methanol in chloroform. Each fraction or pure compounds were evaluated on it's estrogen receptor (ER) binding activity with the fluorescence polarization competitive ERα and ERβ binding assay kit. Cytotoxic assay using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay method was used to establish the cytotoxic activity of the compounds. Four alkyl resorcinols and a dimeric 1,4-benzoquinone, namely belamcandol B (1), 5-pentadec-10'-(Z)-enyl resorcinol (2), 1,3-dihydroxy-5-pentadecylbenzene (3), 5-(heptadec-12'-(Z)-enyl) resorcinol (4) and demethylbelamcandaquinone B (5) were identified with selective binding affinities towards either ERα or ERβ exhibiting selectivity ratio from 0.15-11.9. Alkyl resorcinols (2)-(4) exhibited cytotoxic activity towards HL60 cells with IC50 values from 19.5-22.0 μM. Structural differences between compounds influence the binding affinities to ER subtypes. Further study is needed to establish the agonist or antagonist effect of these compounds on various tissues and to identify if these compounds exert cytotoxic activity through the ERs. When consuming L.pumila as a complementary medicine, careful consideration regarding it's estrogenic compound content should be given due consideration.

Matched MeSH terms: Estrogen Receptor beta/drug effects*
Oestrogen actions contribute to female gender-specific risks in the development of lung carcinoma

Liau CS, Mogan P, Thomas W

J Steroid Biochem Mol Biol, 2021 04;208:105786.
PMID: 33189851 DOI: 10.1016/j.jsbmb.2020.105786

Lung cancer is increasing in incidence particularly among women, associated with a global change in smoking habits. Steroid hormones, particularly oestrogen exert an influence on tumour progression in tissues where their target receptor is expressed. Oestrogen receptor, particularly ERβ is highly expressed in the lung and becomes more highly expressed in lung carcinogenesis. Genes involved in the process of lung carcinoma progression and signalling cascades linked to invasion and angiogenesis are modulated by oestrogen receptors. This review intends to collate recently published evidence identifying a role for oestrogen in the initiation and progression of lung carcinoma and how these two processes are differentially affected by circulating oestrogens both in women and in men. Circulating oestrogens may be a significant risk factor in women's susceptibility to lung carcinoma and also provide an additional approach for more targeted therapy.

Matched MeSH terms: Estrogen Receptor beta/blood*
The expression of sex steroid receptors and sex steroid-synthesizing/metabolizing enzymes in metastasized lymph nodes of prostate cancer

Nakamura Y, Ise K, McNamara KM, Azmahani A, Sato S, Fujishima F, et al.

Hum Pathol, 2019 02;84:124-132.
PMID: 30290162 DOI: 10.1016/j.humpath.2018.09.011

The expression statuses of sex steroid receptors and sex steroid-synthesizing/metabolizing enzymes have been reported in primary prostate cancer lesions, but that in metastatic lymph nodes has remained unknown. Therefore, in this study, we immunolocalized these proteins in primary tumors and paired metastatic lymph nodes of prostate cancer and correlated the findings with clinicopathological factors of individual patients. The expression statuses of AR and ER β was significantly increased in metastatic lymph nodes compared with primary lesions, whereas that of 17βHSD1, 17βHSD2, 17βHSD5, and STS immunoreactivity was decreased in metastatic lymph nodes. In metastatic lymph nodes, the status of 5α2 was significantly correlated with that of AR. In addition, 17βHSD5-, 5α1-, STS-, and EST-positive cases were significantly associated with Gleason score (GS) status (GS > 8 versus GS < 7) in metastatic lymph nodes. Results of our present study did demonstrate that in situ androgen and estrogen metabolism and action play roles in pathophysiology of prostate cancer in metastatic lymph nodes, but these steroidogenic effects could be different from those in primary lesions.

Matched MeSH terms: Estrogen Receptor beta/metabolism
Fulltext The Association of Estrogen Receptor-β Gene Variation With Salt-Sensitive Blood Pressure

Manosroi W, Tan JW, Rariy CM, Sun B, Goodarzi MO, Saxena AR, et al.

J Clin Endocrinol Metab, 2017 11 01;102(11):4124-4135.
PMID: 28938457 DOI: 10.1210/jc.2017-00957

Context: Hypertension in young women is uncommon compared with young men and older women. Estrogen appears to protect most women against hypertension, with incidence increasing after menopause. Because some premenopausal women develop hypertension, estrogen may play a different role in these women. Genetic variations in the estrogen receptor (ER) are associated with cardiovascular disease. ER-β, encoded by ESR2, is the ER predominantly expressed in vascular smooth muscle.
Objective: To determine an association of single nucleotide polymorphisms in ESR2 with salt sensitivity of blood pressure (SSBP) and estrogen status in women.
Methods: Candidate gene association study with ESR2 and SSBP conducted in normotensive and hypertensive women and men in two cohorts: International Hypertensive Pathotype (HyperPATH) (n = 584) (discovery) and Mexican American Hypertension-Insulin Resistance Study (n = 662) (validation). Single nucleotide polymorphisms in ESR1 (ER-α) were also analyzed. Analysis conducted in younger (<51 years, premenopausal, "estrogen-replete") and older women (≥51 years, postmenopausal, "estrogen-deplete"). Men were analyzed to control for aging.
Results: Multivariate analyses of HyperPATH data between variants of ESR2 and SSBP documented that ESR2 rs10144225 minor (risk) allele carriers had a significantly positive association with SSBP driven by estrogen-replete women (β = +4.4 mm Hg per risk allele, P = 0.004). Findings were confirmed in Hypertension Insulin-Resistance Study premenopausal women. HyperPATH cohort analyses revealed risk allele carriers vs noncarriers had increased aldosterone/renin ratios. No associations were detected with ESR1.
Conclusions: The variation at rs10144225 in ESR2 was associated with SSBP in premenopausal women (estrogen-replete) and not in men or postmenopausal women (estrogen-deplete). Inappropriate aldosterone levels on a liberal salt diet may mediate the SSBP.

Matched MeSH terms: Estrogen Receptor beta/genetics*
Fulltext Genetic Predictors of Salt Sensitivity of Blood Pressure: The Additive Impact of 2 Hits in the Same Biological Pathway

Haas AV, En Yee L, Yuan YE, Wong YH, Hopkins PN, Jeunemaitre X, et al.

Hypertension, 2021 Dec;78(6):1809-1817.
PMID: 34757767 DOI: 10.1161/HYPERTENSIONAHA.121.18033

[Figure: see text].

Matched MeSH terms: Estrogen Receptor beta/genetics*
Immunohistochemical detection of phospho-Akt, phospho-BAD, HER2 and oestrogen receptors alpha and beta in Malaysian breast cancer patients

Seow HF, Yip WK, Loh HW, Ithnin H, Por P, Rohaizak M

Pathol Oncol Res, 2010 Jun;16(2):239-48.
PMID: 19882362 DOI: 10.1007/s12253-009-9216-3

Activation of Akt signaling pathway has been documented in various human malignancies, including breast carcinoma. The objective of this study is to determine the incidence of Akt phosphorylation in breast tumours and its relationship with expression of ER-alpha, ER-beta, HER2, Ki-67 and phosphorylated Bcl-2 associated death domain (p-BAD). Immunohistochemical staining was performed to detect these molecules on 43 paraffin-embedded breast tumour tissues with commercially available antibodies. Eighteen (41.9%), 3 (7.0%), 23 (53.5%), 35 (81.4%), 21 (48.8%), 29 (67.4%), and 34 (81.0%) of breast tumours were positive for nuclear ER-alpha, nuclear ER-beta, membranous HER2, cytonuclear p-Akt (Thr308), p-Akt (Ser473), p-BAD and Ki-67, respectively. ER-alpha expression was inversely correlated with HER2 and Ki-67 (P = 0.041 and P = 0.040, respectively). The p-Akt (Ser473) was correlated with increased level of p-BAD (Ser136) (P = 0.012). No relationship of Akt phosphorylation with HER2, ER-alpha or ER-beta was found. The p-Akt (Ser473) immunoreactivity was significantly higher in stage IV than in stage I or II (P = 0.036 or P = 0.009). The higher Ki-67 and lower ER-alpha expression showed an association with patient age of <50 years (P = 0.004) and with positive nodal status (P = 0.033), respectively. Our data suggest that the Akt phosphorylation and inactivation of its downstream target, BAD may play a role in survival of breast cancer cell. This study does not support the simple model of linear HER2/PI3K/Akt pathway in breast cancer.

Matched MeSH terms: Estrogen Receptor beta/genetics; Estrogen Receptor beta/metabolism*
Fulltext Estrogen receptor modulatory effects of germinated brown rice bioactives in the uterus of rats through the regulation of estrogen-induced genes

Muhammad SI, Maznah I, Mahmud RB, Saeed MI, Imam MU, Ishaka A

Drug Des Devel Ther, 2013;7:1409-20.
PMID: 24324328 DOI: 10.2147/DDDT.S50861

The expression of genes regulated by estrogen in the uterus was studied in ovariectomized (OVX) rats treated with germinated brown rice (GBR) bioactives, and compared to Remifemin or estrogen at different doses to identify the regulation of these genes in the uterus and their molecular mechanisms.

Matched MeSH terms: Estrogen Receptor beta/genetics
Estrogen receptor β in Merkel cell carcinoma: its possible roles in pathogenesis

Azmahani A, Nakamura Y, Ishida H, McNamara KM, Fujimura T, Haga T, et al.

Hum Pathol, 2016 10;56:128-33.
PMID: 27343835 DOI: 10.1016/j.humpath.2016.06.005

Sex steroids have been postulated to influence skin development and functions as well as its pathogenesis. MCC occurs in both sexes; however, the specific differences in pathogenesis among sexes have yet to be conclusively defined. The detailed status of sex steroid receptors (AR, PRA and PRB, and ERα, ERβ) are also unknown in MCC patients. We first immunolocalized sex steroid receptors and compared the results with immunolocalization of relevant transcription factors including SOX2, FOXA1, and Bcl-2 and Ki-67 in 18 cases of MCCs. AR, PRA, PRB, ERα, ERβ, Bcl-2, SOX2, and FOXA1 immunoreactivity was evaluated by using the modified H score method, and Ki-67 was quantified using labeling index. ERβ immunoreactivity was markedly present in all the cases of MCC examined, with relatively weak immunoreactivity of ERα, AR, PRA, and PRB. The status of ERβ immunoreactivity was also significantly correlated with Ki-67 labeling index and Bcl-2 score. These results demonstrated that ERβ could be associated with regulation of both cell proliferation and apoptosis in MCCs.

Matched MeSH terms: Estrogen Receptor beta/analysis*
Fulltext Protective role of Mas Cotek (Ficus deltoidea) against the toxic effects of bisphenol A on morphology and sex steroid receptor expression in the rat uterus

Zaid SSM, Othman S, Kassim NM

Biomed Pharmacother, 2021 Aug;140:111757.
PMID: 34044283 DOI: 10.1016/j.biopha.2021.111757

BACKGROUND: Numerous scientific studies have found that young women are at a high risk of reproductive infertility due to their routine exposure to numerous bisphenol A (BPA) products. This risk is highly associated with the production of reactive oxygen species from BPA products. Ficus deltoidea, which has strong antioxidant properties, was selected as a potential protective agent to counter the detrimental effects of BPA in the rat uterus.
METHODS: Female Sprague-Dawley rats were allocated into four groups (n = 8) as follows: (i) the Normal Control group (NC), (ii) the BPA-exposed group (PC), (iii) the group concurrently treated with BPA and F. deltoidea (FC) and (iv) the group treated with F. deltoidea alone (F).
RESULTS: After 6 weeks of concurrent treatment with F. deltoidea, uterine abnormalities in the BPA-exposed rats showed a significant improvement. Specifically, the size of stromal cells increased; interstitial spaces between stromal cells expanded; the histology of the glandular epithelium and the myometrium appeared normal and mitotic figures were present. The suppressive effects of BPA on the expression levels of sex steroid receptors (ERα and ERβ) and the immunity gene C3 were significantly normalised by F. deltoidea treatment. The role of F. deltoidea as an antioxidant agent was proven by the significant reduction in malondialdehyde level in BPA-exposed rats. Moreover, in BPA-exposed rats, concurrent treatment with F. deltoidea could normalise the level of the gonadotropin hormone, which could be associated with an increase in the percentage of rats with a normal oestrous cycle.
CONCLUSION: F. deltoidea has the potential to counter the toxic effects of BPA on the female reproductive system. These protective effects might be due to the phytochemical properties of F. deltoidea. Therefore, future study is warranted to identify the bioactive components that contribute to the protective effects of F. deltoidea.

Matched MeSH terms: Estrogen Receptor beta/genetics
Fulltext Estrogen Receptors in Nonfunctioning Pituitary Neuroendocrine Tumors: Review on Expression and Gonadotroph Functions

Haydar Ali Tajuddin A, Kamaruddin N, Sukor N, Azizan EA, Omar AM

J Endocr Soc, 2020 Dec 01;4(12):bvaa157.
PMID: 33241169 DOI: 10.1210/jendso/bvaa157

Estrogen (17β-estradiol or E2) is a crucial regulator of the synthesis and secretion of pituitary reproductive hormones luteinizing hormone, follicle-stimulating hormone, and prolactin. In this review, we summarize the role of estrogen receptors in nonfunctioning pituitary neuroendocrine tumors (NF-Pitnets), focusing on immunoexpression and gonadotroph cell proliferation and apoptosis. Gonadotroph tumors are the most common subtype of NF-Pitnets. Two major estrogen receptor (ER) isoforms expressed in the pituitary are estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). Overall, estrogen actions are mostly exerted through the ERα isoform on the pituitary. The G protein-coupled estrogen receptor (GPER) located at the plasma membrane may contribute to nongenomic effects of estrogen. Nuclear immunoreactivity for ERα and ERβ was highest among gonadotroph and null cell tumors. Silent corticotroph tumors are the least immunoreactive for both receptors. A significantly elevated ERα expression was observed in macroadenomas compared with microadenomas. ERα and ERβ may act in opposite directions to regulate the Slug-E-cadherin pathway and to affect invasiveness of NF-Pitnets. In the cellular pathway, ERs regulate estrogen-induced proliferation and differentiation and impact several signaling pathways including the MAPK and PI3K/Akt pathway. Estrogen was the first-discovered inducer of pituitary tumor transforming gene 1 that was abundantly expressed in NF-Pitnets. ERα can be a potential biomarker for predicting tumor size and invasiveness as well as therapeutic target for NF-Pitnets. Selective estrogen receptor modulators or antiestrogen may represent as an alternative choice for the treatment of NF-Pitnets.

Matched MeSH terms: Estrogen Receptor beta
Sexual maturation modulates expression of nuclear receptor types in laser-captured single cells of the cichlid (Oreochromis niloticus) pituitary

Kitahashi T, Ogawa S, Soga T, Sakuma Y, Parhar I

Endocrinology, 2007 Dec;148(12):5822-30.
PMID: 17823257

The role of steroid/thyroid hormones in the regulation of endocrine cells at the level of the pituitary has remained unclear. Therefore, using single-cell quantitative real-time PCR, we examined absolute amounts of transcripts for nuclear receptors [estrogen receptors (ERs) alpha, beta, and gamma; androgen receptors (ARs) a and b; glucocorticoid receptors (GRs) 1, 2a, and 2b; and thyroid hormone receptors (TRs) alpha1, alpha2, and beta] in pituitary cells of immature (IM) and mature (M) male tilapia, Oreochromis niloticus. In the two reproductive stages, ACTH cells expressed only ERbeta, whereas all other pituitary cell types expressed ERalpha + beta, and a subpopulation coexpressed ARa, ARb, GR1, GR2b, and TRbeta but lacked ERgamma, GR2a, TRalpha1, and TRalpha2. IM males had high percentages of LH cells (IM 46.0% vs. M 10.0%), GH cells (IM 23.3% vs. M 7.9%), and prolactin cells (IM 68.8% vs. M 6.0%) with ERbeta, and TSH cells (IM 19.2% vs. M 0.0%) and MSH cells (IM 25.6% vs. M 0.0%) with ERalpha + TRbeta. A high percentage of FSH cells in IM males expressed ERbeta (IM 46.9% vs. M 18.8%), and FSH cells in M males showed significantly high GR1 transcripts (IM 76.0 +/- 5.0 vs. M 195.0 +/- 10.7 copies per cell; P < 0.05), suggesting that FSH cells are regulated differently in the two reproductive stages. Coexpression of ERalpha + beta in high percentages of cells of the GH family (GH, IM 43.8% vs. M 14.3%; prolactin, IM 8.3% vs. M 59.7%; somatolactin, IM 22.2% vs. M 42.2%) suggests that the expression of both ERs is important for functionality. Thus, differential coexpression of genes for nuclear receptors in subpopulations of pituitary cell types suggests multiple steroid/thyroid hormone regulatory pathways at the level of the pituitary during the two reproductive stages.

Matched MeSH terms: Estrogen Receptor beta/genetics; Estrogen Receptor beta/metabolism

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