PubMed Health⌕ Search

Biomedical subjects

R T Chatterton

Publications and source records attributed to R T Chatterton.

At least 55 records · Page 3Linked to original sources
PubMed1993

Comparison of maternal serum lipids before and during parturition.

OBJECTIVE: To investigate peripartum progesterone metabolism by measuring its lipid precursors. METHODS: Serum was collected from eight pregnant women not in labor during the third trimester and again during active labor. Samples were analyzed using quantitative spectrophotometric absorbance techniques for apolipoprotein A-1, high-density lipoprotein cholesterol (HDL), and total cholesterol. RESULTS: Remote from labor, the mean gestational age antepartum was 35.6 weeks; during active labor it was 39.2 weeks. The amount of apolipoprotein A-1 present was 182.0 mg/dL before labor and 156.8 mg/dL during active labor; HDL cholesterol was 59.3 mg/dL before labor and 37.5 mg/dL during active labor, and total cholesterol was 226.6 mg/dL before labor and 144.1 mg/dL during active labor. All differences were significant at P < .05. CONCLUSION: Maternal serum lipids associated with progesterone metabolism appear to decrease in the peripartum period. Progesterone metabolism and parturition may be correlated with these lipid changes, thus identifying patients about to enter labor.

Apolipoprotein A-I↗
PubMed1992

Hormone levels in vegetarian and nonvegetarian teenage girls: potential implications for breast cancer risk.

Between September 1984 and June 1985, a total of 75 adolescent girls, 35 vegetarians residing in a Seventh-Day Adventist school and 40 nonvegetarians residing in a private non-Adventist boarding school, underwent measurement of their plasma hormone levels in the follicular and luteal phase of their menstrual cycles as well as dietary intake measured by 3-day food records, medical history, height, and weight. There were no significant differences between vegetarians and nonvegetarians in average age of the girls, weight, body mass index, age at menarche, years since the onset of menstruation, or percentage of girls with ovulatory cycles. Vegetarian girls had significantly higher levels of log follicular estradiol [2.00 +/- 0.27 (SD) versus 1.85 +/- 0.27 pg/ml, P less than or equal to 0.05] and luteal dehydroepiandrosterone sulfate (DHS) (1.88 +/- 0.71 versus 1.45 +/- 0.80 microgram/ml, P less than or equal to 0.05) than nonvegetarian girls. Follicular DHS was higher in vegetarians than in nonvegetarians (1.72 +/- 0.79 versus 1.45 +/- 0.95 microgram/ml), but the difference was not significant. The differences in follicular and luteal DHS, but not the difference in log estradiol, were significant (P less than or equal to 0.05) after controlling for ovulation, smoking, and alcohol intake with multivariable regression analysis. There were no significant differences in testosterone or in percentage free estradiol levels between vegetarians and nonvegetarians. Smoking was significantly associated with follicular and luteal DHS and with percentage free follicular estradiol, while alcohol use was significantly and inversely associated with percentage free follicular estradiol after controlling for other variables. The implications for breast cancer risk are discussed.

Adolescent↗
PubMed1992

Peripheral and not central suppression of ovarian function during osmotic pump infusion of adrenocorticotropin-(1-24) for one menstrual cycle in the cynomolgus monkey and its partial compensation by a transitory elevation of sex hormone-binding globulin levels.

The purpose of our study was to assess the impact of subchronic administration of ACTH-(1-24) on ovarian function in the primate using a repeated measures experimental design. Osmotic pumps that released ACTH-(1-24) at a dose of 67 micrograms/day were implanted sc in four cynomolgus monkeys for one menstrual cycle. The pumps were filled with saline for the two control cycles, one of which preceded and one of which followed peptide infusion. Administration of ACTH-(1-24) elevated cortisol levels in serum 1.6-fold and those in urine 2.2-fold, without affecting adrenal androgen concentrations. In the follicular phase (FP) of the menstrual cycle, infusion of ACTH-(1-24) did not alter serum levels of estradiol, FSH, or LH. However, immunoreactive estrone excretion in urine was decreased by 71% (P less than 0.05), and serum concentrations of sex hormone-binding globulin (SHBG) were increased by 100% (P less than 0.01). In the luteal phase (LP) of the menstrual cycle, infusion of ACTH-(1-24) suppressed levels of serum estradiol by 54% (P less than 0.001), urinary immunoreactive estrone by 72% (P less than 0.05), serum progesterone by 53% (P less than 0.001), and urinary immunoreactive pregnanediol by 71% (P less than 0.01). Serum FSH concentrations were increased during treatment by 100% (P less than 0.001) in LP, but LH concentrations were not altered. Also, serum levels of SHBG returned to control values in the LP. The lengths of menstrual cycles and the lengths of FP or LP were not affected during or after treatment. These data provide evidence that subchronic infusion of ACTH-(1-24) in primates: 1) suppresses estradiol production by the ovarian follicle as well as estradiol and progesterone production by the corpus luteum, 2) compromises ovarian function without concomitant suppression of serum gonadotropin levels, and 3) induces a transitory elevation of SHBG levels in the circulation, which may compensate for reduced estrogen output.

Animals↗
PubMed1992

Effects of subchronic infusion of dehydroepiandrosterone sulfate on serum gonadotropin levels and ovarian function in the cynomolgus monkey.

OBJECTIVE: To assess the impact of elevated adrenal androgen levels on ovarian function in a nonhuman primate using a repeated measures experimental design. DESIGN: Osmotic pumps that released dehydroepiandrosterone sulfate (DHEAS) were implanted subcutaneously in five cynomolgus monkeys (Macaca fascicularis) for one menstrual cycle. The pumps were filled with saline for the two control cycles, one preceding and the other following DHEAS infusion. RESULTS: Administration of DHEAS elevated its levels in serum fourfold and in urine sevenfold, which returned to pretreatment values in the next cycle. Serum concentrations of estradiol (E2) were reduced by 55% during DHEAS administration in both follicular and luteal phases and were still decreased in the following cycle by 69% in follicular phase and 48% in luteal phase (P less than 0.01). Luteal serum progesterone (P) levels were diminished by 52% during treatment and were accompanied by 56% reduction in immunoreactive pregnanediol excretion in urine (P less than 0.05). Serum luteinizing hormone (LH) levels were decreased during DHEAS infusion by 51% in follicular phase and 58% in luteal phase (P less than 0.01) but returned to baseline in the next cycle. Conversely, serum follicle-stimulating hormone (FSH) concentrations were increased during treatment by 70% in follicular phase and 101% in luteal phase and remained increased by 58% in follicular phase of the next cycle (P less than 0.05). Estrone excretion in urine was higher during DHEAS infusion (1.5-fold increase) but was below pretreatment values in the following cycle by 57% in follicular phase and 51% in luteal phase (P less than 0.001). Administration of DHEAS did not change significantly serum levels of sex hormone-binding globulin. The length of menstrual cycles was not affected by increased levels of adrenal androgens either. However, in the cycles that followed DHEAS infusion, follicular phase was prolonged by an average of 9 days, and luteal phase was shortened by an average of 5 days (P less than 0.01). CONCLUSIONS: These data document that subchronically elevated adrenal androgen levels in primates: (1) suppress E2 and P levels, which may affect fertility; (2) differentially affect gonadotropin secretion, decreasing LH and increasing FSH serum concentrations; and (3) result in disturbances of ovarian function that persist for at least one menstrual cycle after normalization of androgen levels.

Animals↗
PubMed1991

Inhibition of estrogen biosynthesis in the rat ovary by anordrin.

The delay in appearance of vaginal cornification associated with administration of anordiol (de-esterified anordrin) in the post-ovulatory period was confirmed. Ovarian tissue incubated in vitro for 2 h on the day which, in normal cycles, would be the day of proestrus produced negligible amounts of estradiol even in the presence of androstenedione and human menopausal gonadotropin, despite the appearance of apparently mature follicles in the ovaries. Ovaries of untreated rats produced significant amounts of estradiol when androstenedione was present. Continued incubation for 3 days resulted in significant estradiol production by ovaries of anordiol-pretreated rats in the presence of androstenedione, but less than that of ovaries of control rats. Granulosa cells of immature rats pretreated with diethylstilbestrol (DES) were unaffected by pretreatment with anordrin, whether anordrin was given before or after DES treatment. Taken together, the results indicate that anordiol inhibits development of the capacity for estrogen secretion in maturing follicles without affecting structural development, but that follicles that grow under the influence of high concentrations of estrogen (DES) are unaffected by the presence of anordrin (which is rapidly converted to anordiol in vivo). The latter result suggests that DES treatment bypasses the anordiol-sensitive step in follicular maturation.

Analysis of Variance↗
PubMed1991

Antiovulatory action of anordrin in the cynomolgus monkey (Macaca fascicularis).

Anordrin (2 alpha, 17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta, 17 beta-diol dipropionate) was studied for its antiovulatory potency in the cynomolgus monkey. Anordrin, administered daily on days 9-13 of the menstrual cycle in doses of 4.0 and 8.0 mg/kg body weight, did not inhibit luteal activity in the cycle in which it was given, but delayed the development of ovarian follicles for 5 to 6 months. When a single low dose (0.1 or 0.2 mg/kg b.w.) was administered during the first 3 days of the menstrual cycle, follicular maturation was delayed such that luteal activity was not observed for an average of 26 and 39 days, respectively, and pregnanediol in the ensuing luteal phases was significantly decreased. Anordrin appears to inhibit follicular development when given during the stage of follicular recruitment.

Animals↗
PubMed1991

Depletion of luteal phase serum progesterone during constant infusion of cortisol phosphate in the cynomolgus monkey.

OBJECTIVE: To study the impact of chronic infusions of cortisol phosphate on ovarian function in the cynomolgus monkey. DESIGN: Cortisol phosphate at doses of 5 or 15 mg/d or saline were infused for periods of up to 8 weeks using subcutaneously implanted osmotic pumps. SETTING: Animals were maintained in the Center for Experimental Animal Resources, Northwestern University. MAIN OUTCOME MEASURES: Serum total and unbound cortisol concentrations, serum total and unbound progesterone (P) concentrations, urinary P metabolites. RESULTS: Mean increases in serum cortisol of 56% and 77% above control levels were achieved. Mean serum P concentrations were not decreased with low-dose cortisol phosphate infusion during the 12 days preceding menses, but mean serum P levels were decreased by 69% to 2.3 ng/mL during high-dose cortisol phosphate infusion. No corresponding decrease in excretion of conjugated immunoreactive P metabolites was found in daily urine samples during cortisol phosphate infusion, suggesting that production rates of P were unaltered by the cortisol phosphate treatment. Unbound serum cortisol increased by a mean of 162% above control levels during high-dose cortisol phosphate infusion, but no increase occurred in the percentage of unbound serum P. CONCLUSIONS: We conclude that elevation of serum cortisol in the range observed in chronically stressed individuals may severely decrease the available P to target organs by displacement of P from plasma proteins but does not inhibit ovarian steroidogenesis or ovulation.

Animals↗
PubMed1990

Comparison of endometrial biopsy and urinary pregnanediol glucuronide concentration in the diagnosis of luteal phase defect.

To determine if pregnanediol glucuronide (PG) excretion is useful in luteal phase assessment, we compared daily first morning urinary PG concentrations during the luteal phase in nine normal and nine deficient cycles. Total luteal pregnanediol excretion (44.1 +/- 11.3 versus 64.0 +/- 11.6 area units +/- SEM) was not different. However, significantly less pregnanediol was excreted by the abnormal group during the 1st 5 days of the luteal phase (12.7 +/- 1.2 versus 18.0 +/- 1.7 area units +/- SEM, respectively). Thus, delayed PG excretion may be characteristic of luteal phase defect and measurement of urinary PG may be useful only if daily samples during the early luteal phase are obtained.

Biopsy↗
PubMed1990

Exercise-induced ovarian dysfunction in the rat.

The effect of treadmill running on estrous cycles was studied in the rat. Additional effects of cortisol acetate treatment and adrenalectomy were studied in both exercising and sedentary rats. Sedentary rats given the vehicle or cortisol acetate, or which had been adrenalectomized, all exhibited estrous cycles with diestrous phases that were uniformly less than 4 days. However exercising rats had extended estrous cycles; 50-62% of cycles were incomplete within 11 days and 78% of rats had cycles with diestrous phases that were more than 4 days long. There were no difference in duration of estrous cycles of running rats that received vehicle, received cortisol acetate, or had been adrenalectomized. We conclude that the running regimen resulted in a delay of the normal ovulatory period in rats, and that this effect of running was not affected by the presence or absence of glucocorticoids.

Adrenalectomy↗
PubMed1989

Anti-uterotrophic and folliculostatic activities of anordiol (2 alpha,17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta,17 beta-diol).

The estrogenicity and antiestrogenicity of the biologically active metabolite of the contraceptive anordrin was investigated for its actions on both the uterus and ovary. Anordiol (30 micrograms), administered s.c. to ovariectomized mice did not significantly increase wet weight, soluble protein content, or DNA content of uteri 72 hours after a single dose. By comparison, 3 micrograms of estradiol-17 beta under the same conditions significantly increased all three parameters of uterine growth. The increments in uterine wet weight, soluble protein content, and DNA content that were induced by estradiol-17 beta were reduced by 50, 71, and 81%, respectively, when 30 micrograms of anordiol was administered with estradiol-17 beta. A 60 micrograms dose of anordiol did not decrease further any of the three parameters. In further evaluation of the uterine response to anordiol an increase in uterine wet weight and soluble protein was observed with both 30 and 90 micrograms doses of anordiol at 12, 24, 36, and 48 hours, but not at 6 or 72 hr after a single s.c. injection. No significant increase in uterine DNA content was observed with either dose at any time. We conclude that anordiol in this assay is an antiestrogen with weak estrogenic activity. Anordiol was further tested to determine its effect on the estrous cycle of the rat. When given on the afternoon of the first day of diestrus in a dose of 0.8 mg/kg body weight in rats with 5-day estrous cycles, it caused an average lengthening of the cycle to 9.1 +/- 2.1 (S.D.) days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Role of proestrous progesterone secretion in suppressing basal pulsatile LH secretion during estrus of the estrous cycle.

These studies examined the mechanisms responsible for the paucity of basal LH pulses during estrus. We confirmed our earlier observations that constant infusion of naloxone during estrus results in the immediate appearance of pulsatile LH secretion during estrus, consisting of LH peak heights and LH interpulse intervals that are similar to those observed during other days of the estrous cycle. We then tested whether the proestrous surge of progesterone was responsible for the suppression of pulsatile LH secretion during estrus. Three treatment regimens were used on proestrus to either block progesterone secretion (pentobarbital) or block its action (progesterone antiserum or the progesterone antagonist, RU 486). After treatment at 12.00 h on proestrus, blood samples were collected during estrus every 10 min for 4 h, and the plasma samples were analyzed for the pattern of LH secretion. Treatment with pentobarbital (35 mg/kg at 12:00 h) blocked the proestrous surges of LH and progesterone and resulted in pulsatile LH secretion during estrus. The LH interpulse interval (72 +/- 7 min) was somewhat slower than that observed in the naloxone-infused animals (54 +/- 8 min). Simultaneous treatment with pentobarbital and progesterone at 12:00 h on proestrus completely prevented the appearance of LH pulses during estrus. Treatment with either progesterone antiserum (0.5 ml, i.v.) or RU 486 (1 mg s.c.) resulted in the initiation of pulsatile LH secretion during estrus. In the RU 486-treated animals, LH peak heights and LH interpulse intervals were similar to those observed in naloxone-infused animals and during other days of the estrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Metabolism and pharmacokinetics of progesterone in the cynomolgus monkey (Macaca fascicularis).

[4-14C]Progesterone was administered to two cycling female monkeys during the luteal phase of the cycle, and blood and urine were sampled over a 24 h period. Progesterone had a volume of distribution of 1.75 +/- 0.3 L/kg, and a plasma elimination clearance of 0.06 +/- 0.03 L/kg/min. In comparison to the human, plasma progesterone binding was greater and progesterone clearance was slower in the cynomolgus monkey. The major unconjugated metabolite in plasma was 20 alpha-hydroxy-4-pregnen-3-one. In urine 6.2% of 14C-steroids were unconjugated, 2.3% of which were [14C]progesterone. Thin-layer chromatography (TLC) of conjugated metabolites in urine revealed that 24% had the mobility of sulfates, 19% that of glucuronides, and 52% were more polar. After hydrolysis of conjugates, a major fraction chromatographed with pregnanediol. However, despite evidence for the presence of a 20 alpha-hydroxyl group, none of the pregnanediol isomers could be identified among these 14C-steroids. Nevertheless, over 80% of urinary metabolites had sufficient analogy to pregnanediol to bind to an antiserum specific for ring D and the C-17 side-chain of pregnanediol.

Animals↗
PubMed1987

Insulin resistance and abnormal ovarian responses to human chorionic gonadotropin in chronically anovulatory women.

We studied the interrelationships between insulin resistance, obesity, and abnormal ovarian androgen secretion in chronically anovulatory women with clinical or biochemical evidence of hyperandrogenism. Four groups of six subjects each were studied: (1) normal weight (within 10% ideal body weight) anovulatory, (2) obese (greater than 120% ideal body weight) anovulatory, (3) normal weight eumenorrheic, and (4) obese eumenorrheic. After dexamethasone suppression, human chorionic gonadotropin (2000 IU/1.5m2 body surface area intramuscularly) was administered to each subject. Serum testosterone levels were subsequently determined hourly for 17 hours. On a separate occasion, an oral glucose tolerance test was administered to five subjects from each group. Serum glucose and immunoreactive insulin levels were determined before and after the ingestion of a standard 100 gm glucose load. As a group, the anovulatory women had higher (p less than 0.05) basal testosterone levels (1005 +/- 97 pg/ml) than did the ovulatory women (241 +/- 21 pg/ml) (values +/- SE). Obesity per se was not associated with increased basal testosterone levels. Testosterone levels rose in response to human chorionic gonadotropin (p less than 0.005) only in obese anovulatory women, reached maximal levels after 3 hours, and subsequently remained stable. Basal immunoreactive insulin levels were elevated (p less than 0.05) only in obese anovulatory women (52.4 +/- 20 microU/ml) compared with obese eumenorrheic (8.7 +/- 1.0 microU/ml), normal weight anovulatory (5.8 +/- 2.4 microU/ml), and normal weight eumenorrheic (4.6 +/- 0.4 microU/ml) women. Similarly, maximal increases in immunoreactive insulin levels after glucose ingestion were significantly greater (p less than 0.01) in obese anovulatory women compared with other groups. Of note is the observation that maximal changes in testosterone observed within the first 3 hours after human chorionic gonadotropin and maximal changes in insulin were correlated (r = 0.91, p less than 0.01). These data suggest that (1) both insulin resistance and an abnormal acute response to human chorionic gonadotropin are seen only in obese anovulatory women and (2) the degree to which these two abnormalities are manifested is clearly correlated. The mechanism(s) responsible for this interrelationship, as well as the underlying cause(s) of these biochemical defects, remain to be elucidated.

Adult↗
PubMed1987

Testosterone fails to prevent skeletal muscle atrophy from glucocorticoids.

This study was undertaken to determine whether testosterone can stimulate muscle growth as well as counteract the muscle wasting caused by excess glucocorticoids. Female rats were divided into four groups: a vehicle (1% carboxymethycellulose)-treated group, a testosterone acetate (Te)-treated group, a cortisol acetate (Co)-treated group, and a Te + Co group. Animals were injected with the steroids (Te, 40 mg/kg body wt; Co, 20 mg/kg body wt) subcutaneously for 12 consecutive days. Absolute gastrocnemius muscle weights were 8% heavier after testosterone treatment, (P less than 0.05), 20% lighter after glucocorticoid treatment, and 18% lighter after both treatments than those of vehicle-treated animals. However, total body weight loss was less in the Te + Co group than in the group receiving just Co. Specific binding of [3H]triamcinolone acetonide, a synthetic glucocorticoid, in femtomoles per milligram gastrocnemius cytosol protein, was similar between the vehicle-treated (52.9 +/- 4.7) and Te-treated (48.9 +/- 3.6) groups. Specific cytosol binding was also depleted to the same extent (to 11-12 fmol/mg protein) by either the Co or Te + Co injections. There was minimal competition by testosterone for glucocorticoid binding; however, most of the displacement was observed in the corticosteroid binder IB form of the activated triamcinolone acetonide-receptor complex on DEAE-cellulose chromatography. We conclude that Te was ineffective in preventing muscle atrophy caused by Co treatment despite its ability to induce muscle growth. The binding specificity studies lead to the conclusion that most of the testosterone and cortisol functioning were occurring primarily through separate receptor systems.

Adrenalectomy↗
PubMed1986

Limited resistance of hypertrophied skeletal muscle to glucocorticoids.

Male hypophysectomized rats were initially assigned to a control or an overloaded group that underwent compensatory hypertrophy of plantaris muscles to steady-state levels following removal of synergistic musculature. Plantaris muscle mass of overloaded animals was higher than that of controls by 38% (391 +/- 8 vs 284 +/- 7 mg) and glucocorticoid cytosol specific binding concentrations, using [3H]triamcinolone acetonide (TA) as the labeled steroid, was also significantly higher in hypertrophied muscles (83.3 +/- 3.9 fmol . mg protein-1) than in control muscles 56.3 +/- 3.9 fmol . mg protein-1). Cortisone acetate (CA) was then administered daily subcutaneously in high, 100 mg; intermediate, 10 mg; or low, 1.0 mg . kg-1 body wt doses. Groups of rats were killed after 1/4, 2 days and 7 days. Absolute muscle mass losses after 7 days of CA treatment were approx 80 mg with high doses and 60 mg with intermediate doses in both hypertrophied and control muscles. The low CA dose did not produce atrophy. The absolute depletion of [3H]TA binding activity with CA treatment was always greater in hypertrophied muscles of high and intermediate dose treated than those of their respective controls, but TA binding capacities remained higher in hypertrophied muscles than in controls at almost all time points in all treatment groups. Unlike previous findings in which the simultaneous initiation of overload prevented glucocorticoid induced muscle wasting, no resistance to the effect of CA treatment was observed when treatment was begun after hypertrophy had occurred.

Animals↗
PubMed1986

Relationships between ovarian morphology, vaginal cytology, serum progesterone, and urinary immunoreactive pregnanediol during the menstrual cycle of the cynomolgus monkey.

Three different indices of ovulation and luteal activity were studied in eight regularly cycling cynomolgus monkeys. A significant relation between changes in serum progesterone and immunoreactive pregnanediol (I-PD) in urine was obtained. The occurrence of ovulation could be determined reliably from a change in the ratio of cornified to basal epithelial cells in vaginal smears, and luteal activity could be assessed reliably from daily measurements of urinary pregnanediol. The time of ovulation could be defined more precisely by daily I-PD radioimmunoassays than by the vaginal smear pattern. Measurements of I-PD also have the advantage of ease and noninvasiveness over serum progesterone determinations. More detailed information about changes in hormonal activities could not be obtained reproducibly from thorough examination of cell types in vaginal smears.

Animals↗