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The importance of androgen receptor variants (AR-Vs) is recognized in prostate cancer. AR-Vs have been the focus of many studies. Expression of AR-Vs has been proposed as a biomarker for resistance to androgen deprivation therapy for metastatic disease. Herein, we show dynamic changes in AR-Vs expression in response to androgen modulation. The C4-2B cell line was exposed to low (10−13 M) and high (10−8 M) androgen (dihydrotestosterone, DHT) levels, with or without flutamide. mRNA and protein expression levels were assessed by qPCR and immunohistochemistry, respectively. We demonstrated that high levels of DHT downregulate AR-FL and AR-Vs. Even though AR-Vs did not present ligand-binding domain, thus were not capable of binding to DHT, they present dynamic changes under androgen treatment. Treatment with flutamide alone or in association with low levels of DHT stimulates growth of prostatic cells. Importantly, we provide evidence that AR-Vs respond differently to androgenic modulation. These findings have implications for a better understanding of the role of AR-Vs in prostate carcinogenesis.

The role of molecular changes in the androgen receptor (AR) as AR variants (AR-Vs) is not clear in the pathophysiology of benign prostatic hyperplasia (BPH) and hormone-naive PCa. The aim of the current work was to identify the presence of AR isoforms in benign tissue and primary PCa, and to evaluate the possible association with tumor aggressiveness and biochemical recurrence in primary PCa. The mRNA levels of full length AR (AR-FL) and AR-Vs (AR-V1, AR-V4 and AR-V7) were measured using RT-qPCR. The protein expression of AR-FL (AR-CTD and AR-NTD) and AR-V7 were evaluated by the H-Score in immunohistochemistry (IHC). All investigated mRNA targets were expressed both in BPH and PCa. AR-FL mRNA levels were similar in both groups. AR-V4 mRNA expression showed higher levels in BPH, and AR-V1 and AR-V7 mRNA expression were higher in PCa. The AR-V7 protein showed a similar H-Score in both groups, while AR-CTD and AR-NTD were higher in nuclei of epithelial cells from BPH. These results support the assumption that these constitutively active isoforms of AR are involved in the pathophysiology of primary PCa and BPH. The role of AR-Vs and their possible modulation by steroid tissue levels in distinct types of prostate tumors needs to be elucidated to help guide the best clinical management of these diseases.

Thyroid cancer and thyroid nodules are more prevalent in women than men, so female sex hormones may have an etiological role in these conditions. There are no data about direct effects of progesterone on thyroid cells, so the aim of the present study was to evaluate progesterone effects in the sodium-iodide symporterNIS, thyroglobulinTG, thyroperoxidaseTPO, andKI-67genes expression, in normal thyroid follicular cells, derived from human tissue.NIS,TG,TPO, andKI-67mRNA expression increased significantly after TSH 20 μUI/mL, respectively: 2.08 times,P<0.0001; 2.39 times,P=0.01; 1.58 times,P=0.0003; and 1.87 times,P<0.0001. In thyroid cells treated with 20 μUI/mL TSH plus 10 nM progesterone, RNA expression ofNIS,TG, andKI-67genes increased, respectively: 1.78 times,P<0.0001; 1.75 times,P=0.037; and 1.95 times,P<0.0001, andTPOmRNA expression also increased, though not significantly (1.77 times,P=0.069). These effects were abolished by mifepristone, an antagonist of progesterone receptor, suggesting that genes involved in thyroid cell function and proliferation are upregulated by progesterone. This work provides evidence that progesterone has a direct effect on thyroid cells, upregulating genes involved in thyroid function and growth.

A Hiperplasia Prostática Benigna (HPB) é um crescimento patológico e não maligno da próstata causada principalmente pela proliferação exacerbada das células epiteliais e, principalmente, estromais. Essa neoplasia benigna acomete a maioria dos homens de idade avançada, sendo a condição crônica mais prevalente entre a população masculina. Como mostrado em estudos, o desenvolvimento prostático é intimamente dependente da interação entre as variantes celulares estromais e epiteliais presentes nesta glândula. Entretanto, a cocultura de ambos os tipos celulares é de difícil estabelecimento, uma vez que os dois tipos celulares têm diferentes características de adesão à placa de cultivo celular.