Proliferative and anti-proliferative effects of dietary levels of phytoestrogens in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases and caspases

<p>Abstract</p> <p>Background</p> <p>Phytoestogens are a group of lipophillic plant compounds that can have estrogenic effects in animals; both tumorigenic and anti-tumorigenic effects have been reported. Prolactin-secreting adenomas are the most prevalent form of pituitary tumors in humans and have been linked to estrogen exposures. We examined the proliferative effects of phytoestrogens on a rat pituitary tumor cell line, GH₃/B₆/F₁₀, originally subcloned from GH₃cells based on its ability to express high levels of the membrane estrogen receptor-α.</p> <p>Methods</p> <p>We measured the proliferative effects of these phytoestrogens using crystal violet staining, the activation of several mitogen-activated protein kinases (MAPKs) and their downstream targets via a quantitative plate immunoassay, and caspase enzymatic activities.</p> <p>Results</p> <p>Four phytoestrogens (coumestrol, daidzein, genistein, and <it>trans</it>-resveratrol) were studied over wide concentration ranges. Except <it>trans</it>-resveratrol, all phytoestrogens increased GH₃/B₆/F₁₀cell proliferation at some concentration relevant to dietary levels. All four phytoestrogens attenuated the proliferative effects of estradiol when administered simultaneously. All phytoestrogens elicited MAPK and downstream target activations, but with time course patterns that often differed from that of estradiol and each other. Using selective antagonists, we determined that MAPKs play a role in the ability of these phytoestrogens to elicit these responses. In addition, except for <it>trans</it>-resveratrol, a serum removal-induced extrinsic apoptotic pathway was blocked by these phytoestrogens.</p> <p>Conclusion</p> <p>Phytoestrogens can block physiological estrogen-induced tumor cell growth <it>in vitro </it>and can also stimulate growth at high dietary concentrations in the absence of endogenous estrogens; these actions are correlated with slightly different signaling response patterns. Consumption of these compounds should be considered in strategies to control endocrine tumor cell growth, such as in the pituitary.</p

Current opinion on the role of testosterone in the development of prostate cancer: a dynamic model

Background: Since the landmark study conducted by Huggins and Hodges in 1941, a failure to distinguish between the role of testosterone in prostate cancer development and progression has led to the prevailing opinion that high levels of testosterone increase the risk of prostate cancer. To date, this claim remains unproven. Presentation of the Hypothesis: We present a novel dynamic mode of the relationship between testosterone and prostate cancer by hypothesizing that the magnitude of age-related declines in testosterone, rather than a static level of testosterone measured at a single point, may trigger and promote the development of prostate cancer. Testing of the Hypothesis: Although not easily testable currently, prospective cohort studies with population-representative samples and repeated measurements of testosterone or retrospective cohorts with stored blood samples from different ages are warranted in future to test the hypothesis. Implications of the Hypothesis: Our dynamic model can satisfactorily explain the observed age patterns of prostate cancer incidence, the apparent conflicts in epidemiological findings on testosterone and risk of prostate cancer, racial disparities in prostate cancer incidence, risk factors associated with prostate cancer, and the role of testosterone in prostate cancer progression. Our dynamic model may also have implications for testosterone replacement therapy

Effect of a single dose of levodopa on sexual response in men and women

From animal research, there is ample evidence for a facilitating effect of dopamine on sexual behavior. In humans, little experimental research has been conducted on the inter-relation between dopamine and sexual response, even less so in women than in men. We investigated the effect of levodopa (100 mg) on sexual response in men and women following a double-blind, placebo-controlled crossover design. Genital and subjective sexual responses were measured as well as somatic motor system activity by means of Achilles tendon (T) reflex modulation. Genital and subjective sexual arousal were not affected by levodopa. However, the drug increased T reflex magnitude in response to sexual stimulation in men, but not in women. These results support the view that dopamine is involved in the energetic aspects of appetitive sexual behavior in men. The observed gender difference in the effect of levodopa is discussed in the perspective of possible dopamine-steroid interactio