Kelulut Honey Improves Folliculogenesis,Steroidogenic, and Aromatase Enzyme Profiles and Ovarian Histomorphology in Letrozole-Induced Polycystic Ovary Syndrome Rats

Polycystic ovary syndrome (PCOS) has been linked to aberrant folliculogenesis and abnormalities in the aromatase enzyme (Cyp19a1) and the steroidogenic enzyme, 17-alpha-hydroxylase (Cyp17a1) expression. It has been demonstrated that Kelulut honey (KH) improves both female and male reproductive system anomalies in animal studies. Here, we examined the effects of isolated and combined KH, metformin, and clomiphene in improving folliculogenesis, aromatase, and steroidogenic enzyme profiles and ovarian histomorphology in letrozole-induced PCOS rats. Letrozole (1 mg/kg/day) was administered to female Sprague–Dawley (SD) rats for 21 days to induce PCOS. PCOS rats were subsequently divided into six experimental groups: untreated, treatment with metformin (500 mg/kg/day), clomiphene (2 mg/kg/day), KH (1 g/kg/day), combined KH (1 g/kg/day) and metformin (500 mg/kg/day), and combined KH (1 g/kg/day) and clomiphene (2 mg/kg/day). All treatments were given orally for 35 days. We found that KH was comparable with clomiphene and metformin in improving the expression of Cyp17a1 and Cyp19a1, apart from enhancing folliculogenesis both histologically and through the expression of folliculogenesis-related genes. Besides, the combination of KH with clomiphene was the most effective treatment in improving the ovarian histomorphology of PCOS rats. The effectiveness of KH in restoring altered folliculogenesis, steroidogenic, and aromatase enzyme profiles in PCOS warrants a future clinical trial to validate its therapeutic effect clinically.     

Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects

BACKGROUND: During pregnancy there is a high demand for docosahexaenoic acid (DHA), which is needed for formation of the fetal brain. Women who do not consume marine foods must synthesize DHA from fatty acid precursors in vegetable foods. OBJECTIVE: We studied sex differences in DHA status and the role of sex hormones. DESIGN: First, DHA status was compared between 72 male and 103 female healthy volunteers who ate the same rigidly controlled diets. Second, the effects of sex hormones were studied in 56 male-to-female transsexual subjects, who were treated with cyproterone acetate alone or randomly assigned to receive oral ethinyl estradiol or transdermal 17beta-estradiol combined with cyproterone acetate, and in 61 female-to-male transsexual subjects, who were treated with testosterone esters or randomly assigned for treatment with the aromatase inhibitor anastrozole or placebo in addition to the testosterone regimen. RESULTS: The proportion of DHA was 15 +/- 4% (x +/- SEM; P < 0.0005) higher in the women than in the men. Among the women, those taking oral contraceptives had 10 +/- 4% (P = 0.08) higher DHA concentrations than did those not taking oral contraceptives. Administration of oral ethinyl estradiol, but not transdermal 17beta-estradiol, increased DHA by 42 +/- 8% (P < 0.0005), whereas the antiandrogen cyproterone acetate did not affect DHA. Parenteral testosterone decreased DHA by 22 +/- 4% (P < 0.0005) in female-to-male transsexual subjects. Anastrozole decreased estradiol concentrations significantly and DHA concentrations nonsignificantly (9 +/- 6%; P = 0.09). CONCLUSION: Estrogens cause higher DHA concentrations in women than in men, probably by upregulating synthesis of DHA from vegetable precursors.     

Effects of androstenedione-herbal supplementation on serum sex hormone concentrations in 30- to 59-year-old men.

The effectiveness of a nutritional supplement designed to enhance serum testosterone concentrations and prevent the formation of dihydrotestosterone and estrogens from the ingested androgens was investigated in healthy 30- to 59-year old men. Subjects were randomly assigned to consume DION (300 mg androstenedione, 150 mg dehydroepiandrosterone, 540 mg saw palmetto, 300 mg indole-3-carbinol, 625 mg chrysin, and 750 mg Tribulus terrestris per day; n = 28) or placebo (n = 27) for 28 days. Serum free testosterone, total testosterone, androstenedione, dihydrotestosterone, estradiol, prostate-specific antigen (PSA), and lipid concentrations were measured before and throughout the 4-week supplementation period. Serum concentrations of total testosterone and PSA were unchanged by supplementation. DION increased (p < 0.05) serum androstenedione (342%), free testosterone (38%), dihydrotestosterone (71%), and estradiol (103%) concentrations. Serum HDL-C concentrations were reduced by 5.0 mg/dL in DION (p < 0.05). Increases in serum free testosterone (r2 = 0.01), androstenedione (r2 = 0.01), dihydrotestosterone (r2 = 0.03), or estradiol (r2 = 0.07) concentrations in DION were not related to age. While the ingestion of androstenedione combined with herbal products increased serum free testosterone concentrations in older men, these herbal products did not prevent the conversion of ingested androstenedione to estradiol and dihydrotestosterone.     

Role of peripheral and central aromatization in the control of gonadotrophin secretion in the male sheep

Both testosterone and its aromatized metabolite, oestradiol-17beta, are known to act centrally on the secretion of GnRH, but the major site of aromatization is not clear as aromatase activities are found in numerous tissues including brain and testis. Here, we tested the importance of central aromatization of testosterone using a non-steroidal aromatase inhibitor, fadrozole. To distinguish between testicular and non-testicular sites, five intact and five testosterone-infused castrated rams (600 microg kg(-1) per 24 h for 3 days) were given four injections of fadrozole (i.m.; 500 microg kg(-1)) at 48, 52, 64 and 68 h relative to the start of testosterone infusion. Control rams (n = 5) received vehicle only. Fadrozole treatment decreased plasma oestradiol-17beta concentrations and increased the LH pulse frequency in both intact rams and testosterone-treated castrates, suggesting that non-testicular sites of aromatization are important in the control of pulsatile LH secretion. To test the importance of central aromatization, intact rams (n = 5) were infused into the third ventricle with vehicle (artificial cerebrospinal fluid) or with fadrozole (20 and 200 microg kg(-1) per day). After two weeks, the same two doses of fadrozole were infused intravenously instead of intracerebrally. Central infusion of fadrozole did not affect plasma oestradiol concentrations but increased LH pulse frequency. Only the highest dose increased LH pulse frequency when infused intravenously. In conclusion, central aromatization is involved in the control of pulsatile LH secretion in male sheep.     

Dual effects of phytoestrogens result in u-shaped dose-response curves

Endocrine disruptors can affect the endocrine system without directly interacting with receptors, for example, by interfering with the synthesis or metabolism of steroid hormones. The aromatase that converts testosterone to 17beta-estradiol is a possible target. In this paper we describe an assay that simultaneously detects aromatase inhibition and estrogenicity. The principle is similar to that of other MCF-7 estrogenicity assays, but with a fixed amount of testosterone added. The endogenous aromatase activity in MCF-7 cells converts some of the testosterone to 17beta-estradiol, which is assayed by quantifying differences in the expression level of the estrogen-induced pS2 mRNA. Potential aromatase inhibitors can be identified by a dose-dependent reduction in the pS2 mRNA expression level after exposure to testosterone and the test compound. Using this assay, we have investigated several compounds, including synthetic chemicals and phytoestrogens, for aromatase inhibition. The phytoestrogens, except genistein, were aromatase inhibitors at low concentrations (< 1 micro M) but estrogenic at higher concentrations (greater than or equal to 1 micro M), resulting in U-shaped dose-response curves. None of the tested synthetic chemicals were aromatase inhibitors. The low-dose aromatase inhibition distinguished phytoestrogens from other estrogenic compounds and may partly explain reports about antiestrogenic properties of phytoestrogens. Aromatase inhibition may play an important role in the protective effects of phytoestrogens against breast cancer.     

An efficient steroid pharmacophore-based strategy to identify new aromatase inhibitors

Aromatase, an enzyme involved in the conversion of androgens into estrogens, is an important target for the endocrine treatment of breast cancer. Aromatase inhibition is usually achieved with steroids structurally related to the substrate of catalysis or, alternatively, with azole non-steroid compounds. Substituted androstenedione derivatives with Δ¹, Δ⁶ and Δ^1,6 unsaturations and 6-alkyl/6-phenyl aliphatic substitutions, are among the most potent steroid aromatase inhibitors known to date. In this paper we have combined the common pharmacophoric and shape features of these molecules into a new pharmacophore model, useful for virtual screening of large compound databases. Small subsets of the best fitting anti-aromatase candidates were extracted from the NCI database and experimentally tested on an in vitro assay with human placental aromatase. New potent aromatase inhibitors were identified such as compounds 8 and 14. Considering the lack of a crystal structure for the aromatase enzyme, this ligand-based method is a valuable tool for the virtual screening of new aromatase inhibitors.     

Ellagic acid,phenolic acids,and flavonoids in Malaysian honey extracts demonstrate in vitro anti-inflammatory activity

Natural honey has been used in traditional medicine of different cultures throughout the world. This study looked into the extraction of Malaysian honey and the evaluation of the anti-inflammatory activity of these extracts. It was hypothesized that honey extracts contain varying amounts of phenolic compounds and that they possess different in vitro anti-inflammatory activities. Honey extracts were analyzed using liquid chromatography–mass spectrometry to identify and compare phenolic compounds, whereas high-performance liquid chromatography was used for their quantification. Subsequently, honey methanol extract (HME) and honey ethyl acetate extract (HEAE) were tested in vitro for their effect on nitric oxide production in stimulated macrophages. The extracts were also tested for their effects on tumor necrosis factor–α (TNF) cytotoxicity in L929 cells. The major phenolics in the extracts were ellagic, gallic, and ferulic acids; myricetin; chlorogenic acid; and caffeic acid. Other compounds found in lower concentrations were hesperetin, p-coumaric acid, chrysin, quercetin, luteolin, and kaempferol. Ellagic acid was the most abundant of the phenolic compounds recorded, with mean concentrations of 3295.83 and 626.74 μg/100 g of honey in HME and HEAE, respectively. The median maximal effective concentrations for in vitro nitric oxide inhibition by HEAE and HME were calculated to be 37.5 and 271.7 μg/mL, respectively. The median maximal effective concentrations for protection from TNF cytotoxicity by HEAE and HME were 168.1 and 235.4 μg/mL, respectively. In conclusion, HEAE exhibited greater activity in vitro, whereas HME contained a higher concentration of phenolic compounds per 100 g of honey.     

Minimal androgenic activity of a new oral contraceptive containing norethindrone acetate and graduated doses of ethinyl estradiol

The pharmacokinetics and androgenic activity of Estrostep, a new oral contraceptive providing low-dose estrogen in a graduated sequence with a constant dose of progestin, were characterized in an open-label, nonrandomized study in 17 normally cycling women treated for three cycles with Estrostep. Women received 1 mg of norethindrone acetate daily combined with 20 microg of ethinyl estradiol daily for the first 5 days (1/20), 30 microg of ethinyl estradiol daily for the next 7 days (1/30), and 35 microg of ethinyl estradiol daily for 9 days (1/35). No medication was given for 7 days in each cycle to allow for withdrawal bleeding. Serial blood samples for the measurement of ethinyl estradiol and norethindrone concentrations were collected on days 5, 12, and 21 of the third treatment cycle for the 1/20, 1/30, and 1/35 dose, respectively. Sex hormone-binding globulin (SHBG) and free testosterone were measured at baseline, on day 1 of cycles 2 and 3 (SHBG only), and on days 5, 12, and 21 of cycle 3. Mean steady-state plasma ethinyl estradiol and norethindrone concentrations increased over cycle 3. The increases in ethinyl estradiol concentrations were proportional to dose. The increases in norethindrone concentrations were related to ethinyl estradiol-dependent increases in SHBG concentrations, which were 218%, 253%, and 296% of baseline values on days 5, 12, and 21, respectively. Mean plasma free testosterone concentrations decreased 47%, 60%, and 64% below baseline on days 5, 12, and 21 of cycle 3, respectively. Graduated ethinyl estradiol doses combined with a constant norethindrone acetate dose progressively increase SHBG and decrease free testosterone, which overrides any theoretic concerns of androgenic activity of norethindrone acetate. Although true androgenic activity can be determined only by assessing endpoints such as acne, hirsutism, and lipids in large controlled trials, the observed changes in circulating SHBG and free testosterone concentrations indicate that Estrostep has little, if any, intrinsic androgenic activity.     

Molecular basis of the inhibition of human aromatase (estrogen synthetase) by flavone and isoflavone phytoestrogens: A site-directed mutagenesis study.

Flavone and isoflavone phytoestrogens are plant chemicals and are known to be competitive inhibitors of cytochrome P450 aromatase with respect to the androgen substrate. Aromatase is the enzyme that converts androgen to estrogen; therefore, these plant chemicals are thought to be capable of modifying the estrogen level in women. In this study, the inhibition profiles of four flavones [chrysin (5, 7-dihydroxyflavone), 7,8-dihydroxyflavone, baicalein (5,6,7-trihydroxyflavone), and galangin (3,5,7-trihydroxyflavone)], two isoflavones [genistein (4,5,7-trihydroxyisoflavone) and biochanin A (5,7-dihydroxy-4-methoxyisoflavone)], one flavanone [naringenin (4, 5,7-trihydroxyflavanone)], and one naphthoflavone (alpha-naphthoflavone) on the wild-type and six human aromatase mutants (I133Y, P308F, D309A, T310S, I395F, and I474Y) were determined. In combination with computer modeling, the binding characteristics and the structure requirement for flavone and isoflavone phytoestrogens to inhibit human aromatase were obtained. These compounds were found to bind to the active site of aromatase in an orientation in which rings A and C mimic rings D and C of the androgen substrate, respectively. This study also provides a molecular basis as to why isoflavones are significantly poorer inhibitors of aromatase than flavones.     

Effect of oral tamoxifen on semen characteristics and serum hormone profile in male bonnet monkeys

The effects of oral tamoxifen were studied at a dose of 0.4 mg/kg per day, on the serum hormones and semen parameters in adult male bonnet monkeys, for a period of 90 days. Honey was used as vehicle. Monkeys were treated with honey for 30 days, followed by tamoxifen from Day 30-120 (90 days). Thereafter the treatment was withdrawn until Day 150 of schedule. Blood samples were drawn at 12 and 24 clock hours at monthly intervals for the analysis of luteinizing hormone, follicle-stimulating hormone and testosterone. Semen samples were also collected for analysis once a month, from Day 0-150 of exposure. Tamoxifen treatment produced a transient but significant increase in circulating gonadotropins, at Day 90 of treatment schedule, corresponding to 60 days of treatment. Whilst serum testosterone levels were normal throughout treatment period, an increase was observed after 30 days of drug withdrawal. No effect of oral tamoxifen was evident on semen parameters, viz., volume, counts, morphology and motility. However, throughout the exposure period to honey, a significant increase was observed in sperm counts without any effect on testosterone levels. The present study suggests that oral tamoxifen has a transient antiestrogenic effect on the serum hormones and no effect on semen parameters of adult nonhuman primate males. It is concluded that bioefficacy of oral tamoxifen may have been reduced due to hepatic metabolism.     

Endocrine and lipid responses to chronic androstenediol-herbal supplementation in 30 to 58 year old men

OBJECTIVE: The effectiveness of an androgenic nutritional supplement designed to enhance serum testosterone concentrations and prevent the formation of dihydrotestosterone and estrogen was investigated in healthy 3 to 58 year old men. DESIGN: Subjects were randomly assigned to consume a nutritional supplement (AND-HB) containing 300-mg androstenediol, 480-mg saw palmetto, 450-mg indole-3-carbinol, 300-mg chrysin, 1,500 mg gamma-linolenic acid and 1.350-mg Tribulus terrestris per day (n = 28), or placebo (n = 27) for 28 days. Subjects were stratified into age groups to represent the fourth (30 year olds, n = 20), fifth (40 year olds, n = 20) and sixth (50 year olds, n = 16) decades of life. MEASUREMENTS: Serum free testosterone, total testosterone, androstenedione, dihydrotestosterone, estradiol, prostate specific antigen and lipid concentrations were measured before supplementation and weekly for four weeks. RESULTS: Basal serum total testosterone, estradiol, and prostate specific antigen (PSA) concentrations were not different between age groups. Basal serum free testosterone concentrations were higher (p < 0.05) in the 30- (70.5 +/- 3.6 pmol/L) than in the 50 year olds (50.8 +/- 4.5 pmol/L). Basal serum androstenedione and dihydrotestosterone (DHT) concentrations were significantly higher in the 30- (for androstenedione and DHT, respectively, 10.4 +/- 0.6 nmol/L and 2198.2 +/- 166.5 pmol/L) than in the 40- (6.8 +/- 0.5 nmol/L and 1736.8 +/- 152.0 pmol/L) or 50 year olds (6.0 +/- 0.7 nmol/L and 1983.7 +/- 147.8 pmol/L). Basal serum hormone concentrations did not differ between the treatment groups. Serum concentrations of total testosterone and PSA were unchanged by supplementation. Ingestion of AND-HB resulted in increased (p < 0.05) serum androstenedione (174%), free testosterone (37%), DHT (57%) and estradiol (86%) throughout the four weeks. There was no relationship between the increases in serum free testosterone, androstenedione, DHT, or estradiol and age (r2 = 0.08, 0.03, 0.05 and 0.02, respectively). Serum HDL-C concentrations were reduced (p < 0.05) by 0.14 mmol/L in AND-HB. CONCLUSIONS: These data indicate that ingestion of androstenediol combined with herbal products does not prevent the formation of estradiol and dihydrotestosterone.     

芳香化酶改变在多囊卵巢综合征发病中的作用

多囊卵巢综合征(PCOS)是发病多因性、临床表现呈多态性的内分泌综合征,主要的临床特征是雄激素过多和持续无排卵。作为卵巢颗粒细胞中催化雄激素转化为雌激素的限速酶,芳香化酶在PCOS中具有什么作用?就PCOS患者卵巢中芳香化酶基因改变,芳香化酶的表达及其活性,芳香化酶抑制剂诱导PCOS模型及芳香化酶抑制剂诱导排卵等研究综述,特别是近年芳香化酶抑制剂在治疗多囊卵巢导致的无排卵性不孕方面的临床试验及应用情况。     

Evaluation of the methoxytriazine herbicide prometon using a short-term fathead minnow reproduction test and a suite of in vitro bioassays

Prometon is one of the most consistently detected herbicides in the U.S. environment. However, no previous assessment of the potential for prometon or related methoxytriazine herbicides to act as endocrine-disrupting chemicals has been conducted. This study used an array of in vitro bioassays to assess whether prometon, atraton, terbumeton, or secbumeton might act as potent (ant)agonists of the aryl hydrocarbon, estrogen, androgen, or glucocorticoid receptors or as aromatase inhibitors or inducers in vitro. Potential effects of prometon were also evaluated using a 21-d fathead minnow reproduction assay. Concentrations of methoxytriazines, as great as 1 mg/L (4.4 microM), did not induce significant dioxin-like responses in H4IIE-luc cells, estrogenic responses in MVLN cells, or androgen or glucocorticoid receptor-mediated responses in MDA-kb2 cells, nor did the methoxytriazines significantly affect aromatase activity in vitro. In the fathead minnow assay, exposure to 20, 200, or 1,000 microg prometon/L significantly reduced the weight of the male fat pad (an androgen-responsive tissue) relative to body weight. Exposure to 20 microg prometon/L significantly increased female plasma testosterone concentrations, but the effect was not observed at greater concentrations. Overall, prometon did not significantly reduce fecundity over the 21-d exposure, nor were other endpoints, including plasma vitellogenin and estradiol concentrations, brain and ovary aromatase activity, and male tubercle index, significantly affected. Evidence from our work suggests that prometon may cause subtle endocrine and/or reproductive effects in fathead minnows, but no clear mechanism of action was observed. The relevance of these effects to hazard assessment for the pesticide is uncertain.     

Reversible antifertility action of testosterone propionate in human males

Seven healthy male volunteers were injected intramuscularly with 25 mg/ day testosterone propionate for sixty days. Sperm counts and volume of semen were recorded at 15 day intervals. The subjects became azoospermic 60 days after the treatment. Sperm counts were restored to pre-treatment levels 150 days after the withdrawal of the treatment. During the period of testosterone administration and recovery, the quantity of semen did not show any variations. Libido and potentia of the subjects was also normal during the experimental period. This study suggests the possibility of using testosterone as an antifertility agent in human males.     

Subjects with impaired glucose tolerance exhibit a high degree of tolerance to honey

The present study compared the relative tolerance to honey and glucose of subjects with impaired glucose tolerance or mild diabetes. Thirty individuals 35-60 years old with a proven parental (mother or father) history of type II diabetes mellitus were subjected simultaneously to an oral glucose tolerance test (GTT) and a honey tolerance test (HTT). Glucose tolerance was found to be impaired in 24 subjects, while six of the subjects were diagnosed as mildly diabetic. All subjects with impaired glucose tolerance exhibited significantly lower plasma glucose concentrations after consumption of honey at all time points of the HTT in comparison to the GTT. The plasma glucose levels in response to honey peaked at 30-60 minutes and showed a rapid decline as compared to that to glucose. Significantly, the high degree of tolerance to honey was recorded in subjects with diabetes as well, indicating a lower glycemic index of honey. Thus, it is evident from the present investigation that honey may prove to be a valuable sugar substitute for subjects with impaired glucose tolerance or mild diabetes.     

Endocrine and Lipid Responses to Chronic Androstenediol-Herbal Supplementation in 30 to 58 Year Old Men

Objective: The effectiveness of an androgenic nutritional supplement designed to enhance serum testosterone concentrations and prevent the formation of dihydrotestosterone and estrogen was investigated in healthy 30 to 58 year old men.

Design: Subjects were randomly assigned to consume a nutritional supplement (AND-HB) containing 300-mg androstenediol, 480-mg saw palmetto, 450-mg indole-3-carbinol, 300-mg chrysin, 1,500 mg gamma-linolenic acid and 1,350-mg Tribulus terrestris per day (n = 28), or placebo (n = 27) for 28 days. Subjects were stratified into age groups to represent the fourth (30 year olds, n = 20), fifth (40 year olds, n = 20) and sixth (50 year olds, n = 16) decades of life.

Measurements: Serum free testosterone, total testosterone, androstenedione, dihydrotestosterone, estradiol, prostate specific antigen and lipid concentrations were measured before supplementation and weekly for four weeks.

Results: Basal serum total testosterone, estradiol, and prostate specific antigen (PSA) concentrations were not different between age groups. Basal serum free testosterone concentrations were higher (p < 0.05) in the 30- (70.5 ± 3.6 pmol/L) than in the 50 year olds (50.8 ± 4.5 pmol/L). Basal serum androstenedione and dihydrotestosterone (DHT) concentrations were significantly higher in the 30- (for androstenedione and DHT, respectively, 10.4 ± 0.6 nmol/L and 2198.2 ± 166.5 pmol/L) than in the 40- (6.8 ± 0.5 nmol/L and 1736.8 ± 152.0 pmol/L) or 50 year olds (6.0 ± 0.7 nmol/L and 1983.7 ± 147.8 pmol/L). Basal serum hormone concentrations did not differ between the treatment groups. Serum concentrations of total testosterone and PSA were unchanged by supplementation. Ingestion of AND-HB resulted in increased (p < 0.05) serum androstenedione (174%), free testosterone (37%), DHT (57%) and estradiol (86%) throughout the four weeks. There was no relationship between the increases in serum free testosterone, androstenedione, DHT, or estradiol and age (r² = 0.08, 0.03, 0.05 and 0.02, respectively). Serum HDL-C concentrations were reduced (p < 0.05) by 0.14 mmol/L in AND-HB.

Conclusions: These data indicate that ingestion of androstenediol combined with herbal products does not prevent the formation of estradiol and dihydrotestosterone.     

Intrauterine Growth Restriction Alters Hippocampal Expression and Chromatin Structure of Cyp19a1 Variants

We evaluated the impact of uteroplacental insufficiency (UPI), and subsequent intrauterine growth restriction (IUGR), on serum testosterone and hippocampal expression of Cyp19a1 variants and aromatase in rats. Additionally, we determined UPI induced histone modification of the promoter regions of Cyp19a1 variants using chromatin immunoprecipitation. Cyp19a1 is the gene encoding the protein aromatase, that catalyzes the biosynthesis of estrogens from androgens and is necessary for masculinization of the brain. IUGR was induced via bilateral uterine artery. UPI increased serum testosterone in day of life 0 (D₀) and day of life 21 (D₂₁) IUGR males to 224% and 299% of control values, respectively. While there was no significant impact of UPI on testosterone in D₀ females, testosterone in D₂₁ IUGR females was 187% of controls. Cyp19a1 variant 1.f and variant II are expressed in the rat hippocampus at D₀ and D₂₁. UPI significantly reduced expression of Cyp19a1 variant 1.f in D₀ males, with no impact in females. Similarly at D₀, UPI reduced expression of aromatase, the protein encoded by Cyp19a1, in males. Dimethylation of H3K4 was increased in the promoter region of variant 1.f (P1.f) and trimethylation of H3K4 was decreased in the promoter region of variant II (PII). At D₂₁, dimethylation of H3K4 is significantly reduced in PII of IUGR males. We conclude that UPI increases serum testosterone and reduces Cyp19a1 variant 1.f expression in the hippocampus of D₀ IUGR males. Additionally, UPI alters the chromatin structure of CYP19a1 at both D₀ and D₂₁.     

Aromatase activity and progesterone metabolism in ovaries of scorbutic mutant rats unable to synthesize ascorbic acid

Aromatase activity and progesterone metabolism were studied in ovaries of scorbutic ODS rats hereditarily unable to synthesize ascorbic acid (AsA). When ODS rats were kept on an AsA-deficient diet for 23 days, the scurvy developed with undetectable levels of AsA in ovaries. A significant increase in ovarian aromatase activity was observed in scorbutic ODS rats. However, there was no difference in the production of testosterone from progesterone between ovaries of scorbutic and ascorbutic ODS rats. These data suggest that AsA may play a role as a modulator of aromatase activity in vivo.     

Effects of anabolic precursors on serum testosterone concentrations and adaptations to resistance training in young men

The effects of androgen precursors, combined with herbal extracts designed to enhance testosterone formation and reduce conversion of androgens to estrogens was studied in young men. Subjects performed 3 days of resistance training per week for 8 weeks. Each day during Weeks 1, 2, 4, 5, 7, and 8, subjects consumed either placebo (PL; n = 10) or a supplement (ANDRO-6; n = 10), which contained daily doses of 300 mg androstenedione, 150 mg DHEA, 750 mg Tribulus terrestris, 625 mg Chrysin, 300 mg Indole-3-carbinol, and 540 mg Saw palmetto. Serum androstenedione concentrations were higher in ANDRO-6 after 2, 5, and 8 weeks (p <.05), while serum concentrations of free and total testosterone were unchanged in both groups. Serum estradiol was elevated at Weeks 2, 5, and 8 in ANDRO-6 (p <.05), and serum estrone was elevated at Weeks 5 and 8 (p <.05). Muscle strength increased (p <.05) similarly from Weeks 0 to 4, and again from Weeks 4 to 8 in both treatment groups. The acute effect of one third of the daily dose of ANDRO-6 and PL was studied in 10 men (23 +/- 4 years). Serum androstenedione concentrations were elevated (p <.05) in ANDRO-6 from 150 to 360 min after ingestion, while serum free or total testosterone concentrations were unchanged. These data provide evidence that the addition of these herbal extracts to androstenedione does not result in increased serum testosterone concentrations, reduce the estrogenic effect of androstenedione, and does not augment the adaptations to resistance training.