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C L Hughes

Publications and source records attributed to C L Hughes.

At least 19 recordsLinked to original sources
PubMed1995

Follicle-stimulating hormone concentrations in relation to active and passive smoking.

OBJECTIVE: To determine the association between various forms of tobacco exposure and ovarian status, as measured by FSH concentrations, in women 38-49 years old. METHODS: Two hundred ninety women between 38-49 years old, who had not had hysterectomy or oophorectomy, completed a self-administered questionnaire that included information on tobacco exposure and had serum FSH levels measured on days 2-4 of the menstrual cycle. Linear regression was used to assess the relation between FSH and tobacco exposure. RESULTS: Controlling for age and other factors, FSH concentrations were 66% higher among current smokers (geometric mean FSH 14.0 mIU/mL) and 39% higher among nonsmokers with passive smoke exposure (11.7 mIU/mL), compared to nonsmoking women without passive smoke exposure (8.4 mIU/mL). The estimated increase in FSH for each year of age was greater for current smokers than for nonsmokers (16 versus 6%, respectively). Ex-smokers did not have higher FSH concentrations, and there was no association between prenatal exposure to tobacco smoke and FSH. CONCLUSION: Both active and passive smoking are associated with elevated FSH concentrations in women 38-49 years old. The effect, limited to women with current exposure, is consistent with a shorter duration of the menopausal transition period.

Adult↗
PubMed1995

Dietary intervention study to assess estrogenicity of dietary soy among postmenopausal women.

We tested the hypothesis that postmenopausal women on a soy-supplemented diet show estrogenic responses. Ninety-seven postmenopausal women were randomized to either a group that was provided with soy foods for 4 weeks or a control group that was instructed to eat as usual. Changes in urinary isoflavone concentrations served as a measure of compliance and phytoestrogen dose. Changes in serum FSH, LH, sex hormone binding globulin, and vaginal cytology were measured to assess estrogenic response. The percentage of vaginal superficial cells (indicative of estrogenicity) increased for 19% of those eating the diet compared with 8% of controls (P = 0.06 when tested by ordinal logistic regression). FSH and LH did not decrease significantly with dietary supplementation as hypothesized, nor did sex hormone binding globulin increase. Little change occurred in endogenous estradiol concentration or body weight during the diet. Women with large increases in urinary isoflavone concentrations were not more likely to show estrogenic responses than were women with more modest increases. On the basis of published estimates of phytoestrogen potency, a 4-week, soy-supplemented diet was expected to have estrogenic effects on the liver and pituitary in postmenopausal women, but estrogenic effects were not seen. At most, there was a small estrogenic effect on vaginal cytology.

Aged↗
PubMed1995

The effect of prenatal exposure to the phytoestrogen genistein on sexual differentiation in rats.

Exposure to naturally occurring estrogens during critical periods of development can alter morphologic and physiologic markers of sexual differentiation. The current experiment characterizes the effects of in utero treatment with genistein, an isoflavonoid phytoestrogen, on birth weight, anogenital distance (AGD) at birth. GnRH stimulated luteinizing hormone (LH) secretion, volume of the sexually dimorphic nucleus in the preoptic area of the hypothalamus (SDN-POA), puberty onset, and vaginal cyclicity. Pregnant Charles River CD rats were injected sc daily on gestation day 16-20 with either 25,000 micrograms genistein (G25), 5,000 micrograms genistein (G5), 5 micrograms diethylstillbestrol (DES), 50 micrograms estradiol benzoate (E), or corn oil alone for controls. Birth weights and anogenital distance was taken and exposed progeny were subsequently used in two experiments. In Experiment 1 intra-atrial catheters were placed in adult castrated rats, GnRH was given iv, serial blood samples were drawn and sera were assayed for LH by radioimmunoassay (RIA). Brains obtained by subsequent decapitation were saved for histology. In Experiment 2, females were monitored for timing of vaginal opening as a marker of puberty onset, and vaginal smears were taken to monitor cyclicity. G25-treated females and DES- and E-treated animals of both sexes had decreased weights at birth compared with controls. G5- and E-treated animals of both sexes and DES males had smaller AGD than controls. No significant differences in pituitary responsiveness to GnRH were found among treatment groups. There was a nonsignificant decrease in SDN-POA volume in G5-treated females while DES- and E-treated females had increased SDN-POA volume compared with controls. G5-treated females had delayed puberty onset, and DES-treated females had atypical vaginal cycles in comparison with controls. The results confirm that prenatal exposure to estrogens in the environment can influence sexual differentiation. Our previous experiments have demonstrated that castrate female rats exposed as neonates to genistein have decreased pituitary responsiveness to GnRH challenge and enlarged SDN-POA volume in comparison with controls. Prenatal genistein at these dosages did not significantly alter these markers. However, genistein did mimic other estrogens' effects on AGD and birth weight and had a unique influence on puberty onset. Not only are genistein's effects different from other estrogens, but dosage and timing of exposure during development appear to be important factors in genistein's ability to modify these end points.

Animals↗
PubMed1994

Serum progesterone for the exclusion of early pregnancy in women at risk for recurrent gestational trophoblastic neoplasia.

OBJECTIVE: To evaluate the utility of the serum progesterone level for discriminating pregnancy from gestational trophoblastic neoplasia. METHODS: Serum progesterone levels were measured in 61 women with histories of trophoblastic disease who developed a re-elevation in hCG during surveillance and underwent a work-up to differentiate pregnancy from gestational trophoblastic neoplasia. Progesterone levels were analyzed in the context of diagnostic outcome (pregnancy versus gestational trophoblastic neoplasia) to identify optimal threshold levels of progesterone to be used for classifying outcome. RESULTS: Of the 61 women, 37 proved to be pregnant and 24 had gestational trophoblastic neoplasia. Progesterone less than 2.5 ng/mL was predictive of trophoblastic malignancy, with a sensitivity of 83% (20 of 24 subjects were classified correctly as having gestational trophoblastic neoplasia) and a specificity of 95% (35 of 37 patients with progesterone levels at or above 2.5 ng/mL were correctly classified as pregnant). Progesterone of at least 10 ng/mL was associated with viable pregnancy in 97% of the cases. Furthermore, the progesterone level predicted outcome regardless of the serum hCG value. CONCLUSION: The serum progesterone level is useful for discriminating early pregnancy from gestational trophoblastic neoplasia.

Adolescent↗
PubMed1993

hCG, progesterone, alpha-fetoprotein, and estradiol in the identification of ectopic pregnancy.

OBJECTIVE: To enhance the laboratory diagnosis of ectopic pregnancy by determining levels of hCG, progesterone, estradiol (E2), and alpha-fetoprotein (AFP). METHODS: Serum samples and medical records were retrospectively analyzed from 100 gynecologic patients for whom quantitative hCG determination had been ordered. Clinical data and levels of hCG, progesterone, E2, and AFP were examined by univariate and multivariate logistic analyses. RESULTS: Progesterone, hCG, and E2 were highest in viable pregnancies, whereas AFP tended to be higher in ectopic pregnancies. A single progesterone value could differentiate between ectopic and viable pregnancy in more than 80% of patients. The combination of all four biochemical markers predicted ectopic pregnancy with 98.5% specificity and 94.5% accuracy. Clinical diagnosis was less than 75% accurate. CONCLUSION: A combination of biochemical markers including hCG, progesterone, E2, and AFP can be superior to a single progesterone level or clinical evaluation in the diagnosis of ectopic pregnancy.

Adult↗
PubMed1992

Anogenital distance at birth as a predictor of volume of the sexually dimorphic nucleus of the preoptic area of the hypothalamus and pituitary responsiveness in castrated adult rats.

Variation in anogenital distance (AGD) in female newborn rats depends upon androgenization secondary to transplacental/transmembraneous testosterone from adjacent intrauterine male siblings. Since the size of the sexually dimorphic nucleus of the preoptic area of the hypothalamus (SDN-POA) and the degree of pituitary sensitivity to GnRH are neuroendocrine markers of neonatal androgenization, we compared these to AGD in castrated adult male and female rats. Compared to 1-day-old female rats with short AGD (less than or equal to 1.4 mm), 1-day-old female rats with long AGD (greater than 1.4 mm) had significantly larger SDN-POA volumes as adults. In contrast, LH secretion following GnRH injection did not differ in the two subgroups. Our results emphasize that some endpoints of central nervous system sexual differentiation in the adult rat are predicted by the appearance of a masculinized genital tract at birth. It follows that the complete evaluation of potential androgenizing agents will require systematic assessment of multiple morphologic and functional endpoints.

Animals↗
PubMed1992

Lactoferrin expression in the mouse reproductive tract during the natural estrous cycle: correlation with circulating estradiol and progesterone.

Lactoferrin (LTF), an iron-binding glycoprotein present in most exocrine secretions and in the secondary granules of polymorphonuclear leucocytes (PMN), is regulated by estrogen in the mouse reproductive tract. We investigated the expression of LTF mRNA and protein during the natural estrous cycle to increase our understanding of how this uterine secretory protein is regulated under physiological conditions. There was a positive correlation between LTF mRNA expression in the genital tract and serum estradiol (E2) concentrations. When E2 peaked in proestrus, LTF mRNA and protein were expressed in the uterus; however, during metestrus, when both E2 and progesterone levels were high, LTF mRNA was expressed, while LTF protein was decreasing. LTF protein expression may be hindered by progesterone or some other local factor in the endometrial epithelium after ovulation. Immunohistochemistry demonstrated two distinct staining patterns for LTF in the vaginal and endometrial epithelium. In one staining pattern, the colorimetric reaction was noted over the cytoplasm, and in the other, the nuclear region stained more intensely. This suggests the possibility that in addition to its known role as a secretory protein, LTF may be transported to the nucleus, serving an autocrine role. Our results also indicated that LTF protein is a useful marker for tracking PMN. Nonproliferating epithelial cells in the vagina and endometrium may synthesize chemotactic and/or adhesion molecules for PMN.

Animals↗
PubMed1991

Relationship of laparoscopic findings to self-report of pelvic pain.

An assessment battery including standardized measures of behavioral and psychosocial factors associated with other chronic pain conditions was administered to 102 women scheduled for laparoscopic surgery. Surgeons who were blinded to the patient's self-reported pain data completed the American Fertility Society classification for endometriosis and adhesions on the basis of observed physical disease. Although American Fertility Society classification scores were significantly related to self-assignment into pain or no-pain groups, the extent of physical disease evaluated by this procedure was not significantly correlated with ratings of pain levels or a number of indexes of impairment. The group of patients with laparoscopically diagnosed pathologic conditions reported higher pain levels and greater interference than the group who reported pain and had negative laparoscopic results; however, some women with observable pathologic conditions reported no pain symptoms.

Female↗
PubMed1991

Reproductive hormone levels in gynecologic oncology patients undergoing surgical castration after spontaneous menopause.

The endocrine function of the ovary after menopause is perhaps less well understood than at any other time in the female life cycle. To evaluate the hormonal function of the ovary further at this stage of life, reproductive hormone levels were measured in 11 postmenopausal women admitted to the gynecologic oncology service for pelvic surgery which would involve bilateral oophorectomy. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, along with estradiol, testosterone, dehydroepiandrosterone sulfate (DHEA-S), and androstenedione levels, were measured preoperatively, on Postoperative Days 1 and 4, and at 6 weeks following surgery. Testosterone and androstenedione levels fell by half in these patients, whereas estradiol levels were unaffected. LH and FSH showed a fall in the immediate postoperative period, with a subsequent return to baseline levels by 6 weeks after surgery. DHEA-S levels were unaffected by surgery. There are no discernible differences in subjective menopausal symptoms postoperatively in postmenopausal women undergoing bilateral oophorectomy compared to their preoperative state. The data show that the long-held but inadequately proven thesis that postmenopausal oophorectomy dramatically reduces androgen levels is in fact true. This is further evidence that the postmenopausal ovary is an important source of potent and potentially aromatizable androgens.

Adult↗
PubMed1991

Acute and subacute effects of naturally occurring estrogens on luteinizing hormone secretion in the ovariectomized rat: Part 1.

Acute pretreatment of ovariectomized rats with genistein (G) alters gonadotropin-releasing hormone-(GnRH)-induced LH secretion in a fashion comparable to estradiol (E2). In the present studies we wished to (A) determine whether G can acutely inhibit tonic LH secretion by oral (po) or intravenous (iv) routes, (B) compare GnRH-induced LH responses following higher iv dose pretreatments with G or E2, and (C) determine effects of G or E2 pretreatments on progesterone (P)-induced secretion of LH. Mature Charles River CD rats were ovariectomized, and 2 to 5 weeks later intraatrial cannulae were placed. Serial blood samples were drawn and LH was measured by RIA. In experiments 1 and 2, G or E2 was administered acutely by gavage or iv, while in experiment 3, G and E2 were given subcutaneously (sc) oil 3 days prior to cannulation and sampling. Acute po administration of vehicle or G (0.1, 1.0, and 10 mg/kg BW) had no effect on tonic LH, while E2 suppressed LH at all doses (0.1, 1.0, and 10 mg/kg BW). Acute iv administration of vehicle and higher doses of G (1 and 10 mg/kg BW) had no effect on tonic LH, while the lowest dose G (0.1 mg/kg BW) and all doses of E2 (0.1, 1, and 10 mg/kg BW) suppressed tonic LH. In the iv-treated rats, GnRH-induced LH secretion was more profoundly suppressed by G at all doses than by E2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Acute and subacute effects of naturally occurring estrogens on luteinizing hormone secretion in the ovariectomized rat: Part 2.

Acute intravenous administration of the phytoestrogen genistein (G) blocks the gonadotropin-releasing hormone-(GnRH)-induced rise of luteinizing hormone (LH) in ovariectomized rats. The present experiments were performed to determine whether subacute administration of G or the mycoestrogens zearalenone and zearalenol would affect GnRH-induced or progesterone-induced LH secretion in ovariectomized rats. Charles River CD rats were ovariectomized and used 2 to 5 weeks later. Blood samples were obtained either via decapitation or via intraatrial cannulae three days after compounds were injected subcutaneously in sesame oil or corn oil vehicle. LH was measured by RIA. Pretreatment with estradiol benzoate suppressed LH levels at 1200 h, while G had no effect. Challenge with progesterone (8 mg/kg BW, sc) evoked LH release at 1600 h in rats pretreated with estradiol benzoate, but LH levels did not change in rats pretreated with G, zearalenone, or zearalenol. While GnRH-induced LH secretion was preserved in rats pretreated with estradiol, no LH response was detected in rats pretreated with the higher dose of G (8 mg/kg BW) or either dose of zearalenol (0.8 mg/kg BW or 8 mg/kg BW). We conclude that in the ovariectomized rat 1) subacute administration of G, zearalenone, or zearalenol do not inhibit tonic LH secretion, 2) G, zearalenone, and zearalenol do not provide "estrogenic priming" for progesterone-induced LH secretion; however, 3) G and zearalenol do block GnRH-induced LH secretion. The seemingly selective neuroendocrine effects of these naturally-occurring dietary estrogens emphasize that actions of each putative estrogen must be characterized for each "estrogenic" endpoint.

Animals↗
PubMed1991

The effect of neonatal exposure to DES and o,p'-DDT on pituitary responsiveness to GnRH in adult castrated rats.

While exposure of vertebrates to estrogens during early development has been shown to alter adult reproductive behavior, neuroanatomy, and neurophysiology, effects on gonadotropin secretion have not been studied. We conducted the present studies to assess the effects of neonatal exposure to xenobiotic estrogens on luteinizing hormone secretion in castrated adult rats. Rat pups were injected with either corn oil, 1 micrograms diethylstilbestrol (DES), or 0.5 mg o,p'-DDT on postnatal days 1 to 10, and castration was performed on day 21. On day 42 of life, GnRH (50 ng/kg) was administered via right heart catheters, and blood was sampled for LH at 0, 5, 10, 15, and 30 min. Neonatal exposure to DES in both males and females significantly decreased basal and GnRH-induced LH secretion throughout the sampling period in castrated adults. o,p'-DDT significantly suppressed initial LH levels and blunted GnRH-induced release in males at the 5 min interval, while in females it had no effect. These data show that early exposure to environmental estrogens alters adult pituitary response to GnRH. Our results suggest that sexually distinct effects of environmental estrogens occur and can be readily demonstrated in this experimental model.

Animals↗
PubMed1991

The effect of neonatal exposure to diethylstilbestrol, genistein, and zearalenone on pituitary responsiveness and sexually dimorphic nucleus volume in the castrated adult rat.

The neonatal hormone environment determines the sexually differentiated pattern of brain growth. Estrogens, derived from intracerebral aromatization of testosterone, promote male sexual central nervous system (CNS) development. Developing animals may also encounter estrogens from plant, fungal, and xenobiotic sources (environmental estrogens). The purpose of this study was to assess the effects of environmental estrogens on the physiology and morphology of the hypothalamus and pituitary. Neonatal rats received injections of either corn oil, 0.1 microgram diethylstilbestrol (DES), 100 micrograms genistein (G100), 1000 micrograms genistein (G1000), 100 micrograms zearalenone (Z100), or 1000 micrograms zearalenone (Z1000) on Days 1-10 of life and were castrated on Day 21. On Day 42, right heart catheters were placed, GnRH (50 ng/kg) was administered, and blood was sampled for LH at 0, 5, 10, 15, and 30 min. Females exposed neonatally to DES, G1000, Z100, and Z1000 showed significantly decreased pituitary responsiveness to GnRH, whereas G100 increased GnRH-induced LH secretion. Males exposed neonatally to G100 also showed increased pituitary response to GnRH, and the remaining estrogen-exposed groups of males exhibited either decreased tonic LH or attenuated GnRH-stimulated LH secretion. The animals were killed by decapitation on Day 49. Volumes of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of the exposed groups were compared. In females, DES, G1000, and Z1000 increased SDN volume; Z100 and G100 had no effect. There was no difference in SDN size among the male groups. These data show that exposure to environmental estrogens early in development alters postpubertal pituitary response to GnRH and "androgenizes" the SDN-POA.

Animals↗
PubMed1991

Determinants of mild fasting hypertriglyceridaemia in non-insulin-dependent diabetes.

Factors contributing to fasting hypertriglyceridaemia were studied in 20 patients with non-insulin-dependent diabetes--nine with normal triglyceride concentrations [fasting triglyceride 0.94 (range 0.58-1.23) mmol l-1] and eleven with mild fasting hypertriglyceridaemia [fasting triglyceride 2.4 (1.82-4.0) mmol l-1]. The patients with hypertriglyceridaemia were more obese [body mass index 29.0 (24.6-33.8) vs. 25.7 (21.9-30.1) kg m-2, P less than 0.05] and demonstrated impaired glucose disposal in response to exogenous insulin at isoglycaemia [insulin sensitivity index, SIp 0.7 (0.27-2.5) vs. 2.4 (0.62-5.1) ml m-2 min per mU l-1, P less than 0.001]. Basal non-esterified fatty acid (NEFA) and glycerol concentrations were higher and were suppressed to a lesser extent during isoglycaemic hyperinsulinaemia. Fasting glucose and apolipoprotein B concentrations were higher in the hypertriglyceridaemic patients, but lipoprotein lipase activities were similar in the two groups. When the effect of obesity was removed (by weight-matching six normotriglyceridaemic with seven hypertriglyceridaemic patients) basal NEFA and glycerol concentrations and the suppression of NEFA in response to insulin remained significantly different between the two groups. We propose that defects in both the glucoregulatory and antilipolytic actions of insulin contribute to mild fasting hypertriglyceridaemia in NIDDM, and that these defects cannot be attributed solely to obesity. These disorders of insulin action may also have important implications for the postprandial metabolism of triglyceride-rich lipoproteins and hence atherogenesis.

Adult↗
PubMed1991

The role of insulin insensitivity and hepatic lipase in the dyslipidaemia of type 2 diabetes.

Fourteen male patients with Type 2 diabetes were studied to identify relationships between insulin-mediated glucose disposal, basal and glucose-stimulated insulin secretion, fasting lipoproteins and apolipoproteins, and the activities of lipoprotein lipase and hepatic lipase. Sensitivity of glucose disposal to exogenous insulin correlated positively with HDL-cholesterol (r = 0.65, p less than 0.05), HDL2-cholesterol (r = 0.59, p less than 0.05), and apolipoprotein A1 (r = 0.57, p less than 0.05) and negatively with apolipoprotein B (r = -0.53, p less than 0.05) and total: HDL-cholesterol ratio (r = -0.68, p less than 0.01). Fasting C-peptide correlated negatively with HDL-cholesterol (r = -0.76, p less than 0.01), HDL2-cholesterol (r = -0.80, p less than 0.001) and apoprotein A1 (r = -0.56, p less than 0.05) and positively with total: HDL-cholesterol ratio (r = 0.64, p less than 0.05). Neither fasting plasma glucose nor the indices of stimulated insulin secretion (glucose-stimulated plasma insulin and C-peptide) were related to any of the lipoprotein measures. Insulin insensitivity and hyperinsulinaemia were both associated with higher levels of hepatic lipase activity but did not influence lipoprotein lipase activity. In multiple linear regression analysis, hepatic lipase activity was related to HDL-cholesterol independent of insulin insensitivity. In addition, fasting C-peptide alone accounted for 70% of the variance in hepatic lipase activity and this was independent of insulin sensitivity and body mass index. We propose that the abnormalities of HDL-cholesterol in Type 2 diabetes are closely related to enhanced hepatic lipase activity brought about by increased insulin secretion which, in turn, is secondary to the defect in insulin action.

Adult↗
PubMed1991

Adjunctive leuprolide therapy does not improve cycle fecundity in controlled ovarian hyperstimulation and intrauterine insemination of subfertile women.

Problems arising from controlled ovarian hyperstimulation for intrauterine insemination, such as premature luteinization and asynchronous ovarian follicular development, are identical to those encountered with controlled ovarian hyperstimulation for in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). It has been suggested that the adjunctive use of GnRH agonists for controlled ovarian hyperstimulation improves the efficiency of GIFT and IVF cycles. We hypothesized that adjunctive use of leuprolide acetate, a GnRH agonist, would have a similarly beneficial effect on cycle quality and cycle fecundity in subfertile women treated with controlled ovarian hyperstimulation and intrauterine insemination. We randomly assigned the first cycle of controlled ovarian hyperstimulation and intrauterine insemination for each of 97 subfertile women to include either human menopausal gonadotropins (hMGs) alone or hMGs following midluteal pre-treatment with leuprolide. If a pregnancy did not occur in the first cycle, the woman was given the other treatment in the second cycle. Although the cycles that included leuprolide required a larger amount of hMGs and more days of stimulation per cycle, the mean estradiol concentrations and numbers of follicles were not different. Despite prevention of premature luteinization with leuprolide, the cycle fecundity was not different between groups (0.11 with adjunctive leuprolide treatment and 0.22 with hMGs alone). We conclude that in unselected subfertile patients, the adjunctive use of leuprolide for controlled ovarian hyperstimulation and intrauterine insemination does not improve cycle fecundity compared with treatment cycles that do not include adjunctive leuprolide therapy.

Adult↗
PubMed1990

Synthetic estrogens suppress granulosa cell progesterone production in vitro.

We evaluated the effect of commonly used pharmaceutical estrogens and zeranol, an estrogenic growth-promoting agent used in livestock, on progesterone (P) production by cultures of highly differentiated porcine granulosa cells (GC). The compounds were added to GC cultures over a dose range of 10(-8) to 10(-5) M with P and cell protein measured after 24 h. P production was suppressed by estradiol (minimal suppressive dose: 10(-7) M; maximal suppression to 11% of control), ethinyl estradiol (10(-7) M, 15%), diethylstilbestrol (10(-5) M, 72%), clomiphene citrate (10(-6) M, 30%), nafoxidine (10(-7) M, 33%), tamoxifen (10(-6) M, 37%), and zeranol (10(-5) M, 83%). P production was not suppressed by mestranol. GC protein was suppressed by estradiol, ethinyl estradiol, nafoxidine, and zeranol. These data suggest that synthetic estrogens have the potential to suppress luteal P production by a mechanism unrelated to the usual measures of estrogenicity.

Animals↗