Soy consumption and phytoestrogens: effect on serum prostate specific antigen when blood lipids and oxidized low-density lipoprotein are reduced in hyperlipidemic men

PURPOSE: Herbal remedies high in phytoestrogens have been shown to reduce serum prostate specific antigen (PSA) and have been proposed as a treatment for prostate cancer. Soy proteins used to lower serum cholesterol are rich sources of phytoestrogens. Therefore, we assessed the effect of soy consumption on serum PSA in men who had participated in cholesterol lowering studies. MATERIALS AND METHODS: For 3 to 4 weeks 46 healthy middle-aged men with a range of starting PSA values took soy (mean 44 gm. soy protein daily, 116 mg. isoflavones daily) or control foods, and a subgroup of men took a lower level of soy supplements for 3 months. PSA was measured at the start and end of each treatment. RESULTS: Soy had no significant effect on serum total or free PSA, independent of PSA starting value or isoflavone intake. The lack of effect on PSA was seen, although soy intake was sufficient to reduce low-density lipoprotein cholesterol (5.8 +/- 2.2%, p = 0.012), the estimated coronary heart disease risk (6.1 +/- 2.8% for 10 years, p = 0.032) and the serum concentration of oxidized low-density lipoprotein measured as conjugated dienes (9.5 +/- 3.4%, p = 0.008) in the 3 to 4-week study. In addition, the lack of effect of soy on PSA persisted for the 3 months of the extended study. CONCLUSIONS: At levels of soy intake which reduce low-density lipoprotein cholesterol any potential benefits of soy consumption on prostate cancer are likely to occur for reasons other than alterations in hormone activity.     

<Emphasis Type="Bold">Reproductive Endocrinology:</Emphasis> Uterine Perfusion and Hormonal Pattern in Patients with Polycystic Ovary Syndrome

Purpose: To evaluate whether polycystic ovary syndrome (PCOS) patients with different pulsatility index (PI) of uterine artery showed differences in their hormonal pattern. Methods: Eighty-eight PCOS-affected patients and 15 controls were submitted to Doppler flow measurement of uterine artery; LH, FSH PRL, estradiol, and androgens concentration determination; and BMI evaluation during early follicular phase. Results: The mean PI of uterine artery of PCOS patients was significantly higher than control group (2.97 ± 0.9 vs. 1.89 ± 0.2 respectively). The distribution of the PI'values was significantly different in the PCOS-affected patients and in control group. The plasma levels of DHEAS and BMI were significantly higher in PCOS patients with PI 3 than in PCOS patients with PI < 3. Conclusion: High resistance in the uterine artery is present in PCOS patients, but a wide range PI values of uterine artery is present. BMI and DHEAS seem to be factors interfering with uterine perfusion.     

Effect of androgen deprivation on penile ultrastructure

Aim: To investigate the ultrastructural changes of penile corpus cavernosum and tunica albuginea in rats treated with castration or finasteride. Methods: Eighteen male Sprague-Dawley rats of nine weeks old were randomly divided into three groups with 6 rats each. Group A served as the control, Group B was castrated and Group C, treated with finasteride. Four weeks later, rats were anesthetized and blood samples obtained for the determination of serum testosterone (T) and dihydrotestosterone (DHT) levels; penile tissues were taken for scanning electron microscopy. Results: The T, free T and DHT levels in Group B and the DHT level in Group C were significantly lower than those in Group A (P<0.05). The tunica albuginea was significantly thinner in Group B than that in Group A (P<0.05), but there was no significant difference between Group C and Group A (P>0.05). Elastic fibers in the tunica albuginea of Group A were very rich and arranged regularly and undulatedly, but in Group B, most of the elastic fibers     

The feasibility of quantitative analysis of androgen metabolism by use of single dermal papillae from human hair follicles

Androgenetic alopecia (AGA) is a dihydrotestosterone-mediated process, characterized by continuous miniaturization of androgen sensitive hair follicles (HF). Although increased 5 alpha-reductase (5aR) activity in affected HF is a key feature in the pathogenesis of AGA, only little is known about the in vivo expression of 5aR within AGA-affected HF. Recent studies have shown that the dermal papilla (DP) is the predominant site of type 2 5aR expression within the human HF, but direct measurements of 5aR activity in intact DP of AGA-affected HF have not been reported so far, mainly because of technical problems. Hence there is a need for a reliable and sensitive method of measuring 5aR activity in fresh tissues. As a novel approach, we used freshly isolated, intact DP and a highly sensitive HPLC-radiomatic flow scintillation system to measure 5aR. In this way we were able to measure 5aR even in small DPs from miniaturized HF. Our results show that DP from the occipital scalp express ex vivo considerable amounts of 5aR activity, but the measurable enzyme activities of individual DP differ considerably. Therefore the use of only one or two DP is at present not a reliable tool to analyze 5aR activity ex vivo.     

Transplantable human prostatic carcinoma (PC-82) in athymic nude mice: I. Hormone dependence and the concentration of androgens in plasma and tumor tissue

This paper is the first part of a series of three describing a number of observations made on the PC-82 human prostatic carcinoma, xenografted into nude mice. The previously described androgen-dependence, one of the main properties of this tumor, has been the subject of subsequent studies. The impact of hormonal manipulation on the growth of the tumor and on plasma and tissue concentrations of androgens is discussed in this first part of the series. The great variability of plasma testosterone (T) levels in intact male mice (range: 1-90 nmol/liter) has been levelled out by the use of T-containing Silastic implants, resulting in levels ranging from 18 to 35 nmol/liter. Moreover, this route of administration also facilitated hormonal manipulation of tumor bearing mice. Androgen withdrawal from male mice with growing PC-82 tumors caused 80% tumor regression at ten weeks after androgen deprivation; the decline of the tumor volume followed a biphasic course. Delayed androgen substitution in castrated male mice grafted with PC-82 30 days before resulted in growth of the tumor tissue. This indicates that cells do not die and keep the capability to respond to androgens. It was concluded that the growth of the PC-82 tumor is not compatible with plasma T levels lower than 1 nmol/liter. Variable concentrations of endogenous T and dihydrotestosterone (DHT) were detected in total homogenates of PC-82 tumor tissue. Androgen withdrawal from T-implanted, tumor-bearing female mice caused a rapid reduction (90% within one day) of the tissue-T and a slower decline (up to 90% within seven to ten days) of tissue-DHT concentrations.     

Plasma androgens and oestradiol during oral glucose tolerance test in patients with polycystic ovaries

Hyperinsulinaemia is common patients with polycystic ovaries (PCO), and a relationship between hyperinsulinaemia and hyperandrogenaemia has been suggested. We studied the effect of increased circulating insulin in response to an oral glucose tolerance test (OGTT) on plasma levels of androgens and oestradiol in PCO patients and in healthy control subjects. A 75 g, 3 h oral glucose tolerance test (OGTT) was performed in eight non-obese and seven obese PCO patients, and in 10 non-obese control subjects. An additional group of five women were fasting during the study period. The increase in insulin concentration was higher in obese and non-obese PCO patients than in non-obese control subjects, and the peak values were observed at 30 or 60 min. In the fasting control subjects, the mean concentration of androstenedione decreased slightly due to a diurnal variation. During the OGTT, mean concentrations of androstenedione decreased in all groups at 30 min, after which a slight increase was observed in PCO patients and a plateau in control subjects. Similarly, mean testosterone increased after an initial decrease in obese PCO patients whereas no change was found in non-obese PCO patients. No statistically significant differences were found in the responses of androstenedione or testosterone levels to OGTT in obese or non-obese PCO patients compared to normals. No significant responses of plasma oestradiol levels to OGTT were found. These findings failed to demonstrate any significantly abnormal acute androgen responses to OGTT-stimulated hyperinsulinaemia in PCO patients, but did not exclude possible long-term effects of hyperinsulinaemia.     

Development of male gender identity/role and a sexual orientation towards women in a 46,XY subject with an incomplete form of the androgen insensitivity syndrome

Transsexualism and homosexuality have been theorized to originate in the male from insufficient androgenization of the brain. For verification of this hypothesis clinical science must rely on subjects with an abnormal prenatal/perinatal endocrine history. A case of a 33-year-old 46,XY subject with an incomplete form of androgen insensitivity syndrome (AIS) is presented. In adulthood the only genital sign of masculinization is a clitoris of 4 cm; the vagina is normal size. The diagnosis AIS was verified by androgen receptor studies. At birth there was confusion as to the sex of the newborn. Originally, the subject was assigned to the male sex, but this decision was reversed 5 days after birth and the subject was reared as a girl. At age 30 the subject applied for gender reassignment treatment to the male sex. Upon psychological evaluation the gender identity was unambiguously male and the sexual orientation was exclusively towards women. The estrogen feedback effect on LH, regarded by some as a marker of the sexual differentiation of the neuroendocrinium was negative before orchiectomy but positive after orchiectomy. Our observation demonstrates that in 46,XY subjects a male gender identity and a sexual orientation towards women can develop with a strikingly lower-than-normal level of biological action of androgens.     

Inhibition of Sα-reductase does not simulate the effects of androgen deprivation on porphyrin metabolism by Harderian glands from the male Syrian hamster

As 5 alpha-reductase is involved in the metabolism of indolamines in the Harderian glands of Syrian hamsters, we have compared the effects of androgen deprivation and the administration of the potent 5 alpha-reductase inhibitor N,N-diethyl-4-methoxy-3-oxo-4-aza-5-androstene-17-carboxamida on Harderian porphyrin metabolism. Ten days after castration, porphyrin levels had increased to 40 times the values of intact hamsters. However, the inhibition of 5 alpha-reductase, which resulted in a significant decrease in the weight of accessory sex glands, did not modify porphyrin concentrations within the Harderian glands. It is concluded that, contrary to the situation for indolamine metabolism, testosterone per se is the main androgen involved in the sexual differences observed in Harderian porphyrin metabolism.     

Unique distribution of aromatase in the human brain: In vivo studies with PET and [N‐methyl‐11C]vorozole

Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N‐methyl‐¹¹C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90‐min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (V_T) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced V_T in all regions, though the size of the reduction was region‐dependent, ranging from ～70% blocking in thalamus andpreoptic area to ～10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage forthe noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain. Synapse 64:801–807, 2010. © 2010 Wiley‐Liss, Inc.     

生理水平的雄激素对亚急性衰老小鼠学习记忆能力的影响

目的探讨生理剂量的外源性丙酸睾酮对亚急性衰老小鼠学习记忆能力的影响。方法将C57BL/6J雄性小鼠38只随机分为对照组(10只)、去势组(10只)、D半乳糖组(9只)、丙酸睾酮组(9只),3个月后对各组小鼠进行水迷宫和避暗穿梭实验,检测脑、肝脏组织的丙二醛、超氧化物歧化酶(SOD)水平,并由Nissl染色观测海马神经元的变化情况。结果去势组小鼠各项行为学指标均劣于对照组,大脑和肝脏的丙二醛水平明显升高,SOD水平明显下降(P0.05),大脑海马CA1区结构松散,神经元数量明显减少(P0.01);与去势组比较,D半乳糖组的行为学指标进一步恶化,大脑丙二醛水平明显升高,SOD水平明显下降,大脑海马CA1区结构紊乱,神经元丢失严重(P0.05);而丙酸睾酮组的上述各项指标与对照组比较,差异无统计学意义。结论雄激素可以逆转亚急性衰老小鼠学习记忆能力的衰退。降低体内氧自由基水平,改善大脑海马CA1区形态,增加CA1区神经元数量,可能是其机制之一。