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Martin Hill

Publications and source records attributed to Martin Hill.

43 records · Page 3Linked to original sources

Association of insulin gene VNTR polymorphism with polycystic ovary syndrome.

Variability in the number of tandem repeats of the insulin gene (INS VNTR) is known to influence several phenotypes, including polycystic ovary syndrome (PCOS), diabetes mellitus type 1, diabetes mellitus type 2, and birth weight. The presence of the class III allele of INS VNTR has been reported to be protective in diabetes mellitus type 1, but in contrary it increases the disease risk of PCOS and diabetes mellitus type 2. PCOS is a very common endocrinopathy in women of reproductive age. The etiology of PCOS is uncertain, but family history of this syndrome suggests a major genetic cause. The aim of this pilot study was to investigate the possible association of INS VNTR polymorphism with PCOS in Czech women. In PCOS, significantly higher WHR, BMI, G(0), G(180), I(30), Cp(0), Cp(30), Cp(60), AUC-I, AUC-Cp, and insulinogenic index and significantly lower AUC-G/AUC-I were found. No significant differences in INS VNTR genotype, phenotype, or allele frequencies were found between PCOS and controls. In spite of several differences in anthropometric and biochemical parameters (abdominal fat localization, increased beta-cell function, and lower insulin sensitivity in PCOS women), no effect of INS VNTR polymorphism was found on insulin secretion, insulin action, or any other screened parameter.

Base Sequence↗

Sex- and age-related changes in epitestosterone in relation to pregnenolone sulfate and testosterone in normal subjects.

Epitestosterone has been demonstrated to act at various levels as a weak antiandrogen. So far, its serum levels have been followed up only in males. Epitestosterone and its major circulating precursor pregnenolone sulfate and T were measured in serum from 211 healthy women and 386 men to find out whether serum concentrations of epitestosterone are sufficient to exert its antiandrogenic actions. In women, epitestosterone exhibited a maximum around 20 yr of age, followed by a continuous decline up to menopause and by a further increase in the postmenopause. In men, maximum epitestosterone levels were detected at around 35 yr of age, followed by a continuous decrease. Pregnenolone sulfate levels in women reached their maximum at about age 32 yr and then declined continuously, and in males the maximum was reached about 5 yr earlier and then remained nearly constant. Epitestosterone correlated with pregnenolone sulfate only in males. In both sexes a sharp decrease of the epitestosterone/T ratio around puberty occurred. In conclusion, concentrations of epitestosterone and pregnenolone sulfate are age dependent and, at least in prepubertal boys and girls, epitestosterone reaches or even exceeds the concentrations of T, thus supporting its role as an endogenous antiandrogen. The dissimilarities in the course of epitestosterone levels through the lifespan of men and women and its relation to pregnenolone sulfate concentrations raise the question of the contribution of the adrenals and gonads to the production of both steroids and even to the uniformity of the mechanism of epitestosterone formation.

Adolescent↗

Levels of testosterone, allopregnanolone and homocysteine in severe hypothyroidism.

Hypothyroidism is very often associated with cardiovascular diseases and neurological complications. Recently, homocysteine has been studied as an independent risk factor for atherosclerosis which negatively affects vascular endothelial cells. Because homocysteine metabolism is related to thyroid and steroid hormones, we studied these relationships in severe hypothyroidism and in euthyroid state. Homocysteine, testosterone and allopregnanolone concentrations were measured in the fasting plasma from 16 women who underwent total thyroidectomy, and who were either hypothyroid or euthyroid. Although all women used oral contraceptives, they were not protected against hyperhomocysteinemia during hypothyroid state. With the normalization of thyroid hormone concentrations homocysteine levels decreased to normal levels. There was a positive correlation between testosterone and homocysteine in the euthyroid state which suggests that not only estrogens but also androgen state should be considered in future studies on homocysteine.

Adolescent↗

Apolipoprotein E gene determines serum testosterone and dehydroepiandrosterone levels in postmenopausal women.

OBJECTIVE: Apolipoprotein E (ApoE) is believed to play an important role in lipid metabolism and has been found to be related to diseases associated with ageing, the important characteristic of which is decline in circulating sex steroids, including androgen. DESIGN: To find the relationships of levels of serum testosterone and its precursor, dehydroepiandrosterone (DHEA), to ApoE polymorphism in 113 postmenopausal Caucasian women. METHODS: The ApoE genotype was assessed by polymerase chain reaction and CfoI endonuclease digestion. ApoE genotype distribution was as follows: E2/3, 15%; E3/3, 71.7%; E2/4, 1.8%; E3/4, 10.6; and E4/4, 0.89%. The differences in serum androgen levels between genotypes were evaluated by ANCOVA and least significant difference (LSD) multiple comparisons test after adjustment for body mass index, age and/or years since menopause. RESULTS: Significant intergroup differences between the most frequent allele combination (2/3, 3/3 and 3/4) in serum DHEA levels were found (P<0.05, ANCOVA). DHEA levels were higher in women with the E3/4 allele combination than in the E3/3 genotype (P<0.01, LSD multiple comparisons). In serum testosterone levels, borderline intergroup differences were found (P<0.07, ANCOVA). Higher testosterone levels were found in the E3/4 allele combination as compared with E3/3 (P<0.05, LSD multiple comparisons). Dose effect of E4 allele analysis indicated higher serum DHEA and testosterone levels in women with the E4 allele present than in women with the E4 allele absent (P<0.003 for DHEA, P<0.007 for testosterone, ANCOVA). CONCLUSIONS: Circulating testosterone and DHEA are associated with the ApoE genotype, which may render women carrying the allele E4 more susceptible to the development of some diseases associated with ageing and menopause [corrected].

Aged↗

Insulin sensitivity and beta-cell function in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate insulin sensitivity (IS) and beta-cell function (beta F) in lean and obese women with polycystic ovary syndrome (PCOS), either separately or by using a disposition index (DI). RESEARCH DESIGN AND METHODS: A total of 64 women with PCOS and 20 healthy women were examined by anthropometry, oral glucose tolerance tests (OGTTs), and insulin tolerance tests. Statistical analysis used one-way ANOVA, Kruskal-Wallis, and Mann-Whitney U tests, as appropriate. RESULTS: A significantly higher waist-to-hip ratio (P < 0.0001) was found in both lean and obese women with PCOS. Higher basal blood glucose (P < 0.004) and blood glucose values at 3 h of OGTT (P < 0.008) were found in lean and obese PCOS subjects in comparison with control subjects. Insulin resistance by homeostasis model assessment (P < 0.007) was significantly higher in obese PCOS than in control or lean PCOS subjects. Early-phase insulin secretion (insulinogenic index [Delta I/Delta G(30-0), where I is insulin and G is glucose]; P < 0.0007) was significantly higher in both lean and obese PCOS subjects than in healthy women. All tested combinations of parameters of IS and beta F (DIs) followed a physiological hyperbolic relationship. Significantly lower values of the fasting state-derived DIs were found (all P < 0.05) in obese PCOS subjects. Significantly higher values of all of these indexes derived from nonfasting values were found in lean PCOS as compared with control and obese PCOS subjects (all P < 10(-3)). CONCLUSIONS: Increased beta F was found even in lean individuals with PCOS. Insulin hypersecretion is thus probably connected to the pathogenesis of PCOS.

Adult↗

Gas chromatographic-mass spectrometric identification of 16alpha-hydroxy-dehydroepiandrosterone in human seminal plasma.

16alpha-hydroxydehydroepiandrosterone was for the first time detected in human seminal plasma by using a combination of extraction, solvent partition, HPLC separation and final quantification by GC-MS as pentafluorobenzyloxime trimethylsilyl ether derivative in SIM mode. Three effective mass fragments m/z 266, 356 and 446 were followed. The concentration of 16alpha-hydroxydehydroepiandrosterone amounted in average 1.06 nmol/l, being lower but close to- the product of concurrent DHEA metabolism, 7-hydroxydehydroepiandrosterone isomers, found recently in seminal plasma.

Chromatography, High Pressure Liquid↗