Biomedical subjects

R T Chatterton

Publications and source records attributed to R T Chatterton.

At least 37 records · Page 2Linked to original sources

PubMed1997

Relationship of dehydroepiandrosterone and cortisol in disease.

Does dehydroepiandrosterone act as an adrenal hormone in humans to maintain cortisol homeostasis by serving as a cortisol antagonist? If so, dehydroepiandrosterone might block the development of the diverse pathological processes potentiated by prolonged cortisol hyperactivity. And the plasma concentrations of total dehydroepiandrosterone and total cortisol, expressed as a C/D ratio, would have an important influence on the development of age-related pathology in diseases exacerbated by cortisol hyperactivity. Several major age-related diseases, designated as cortisol-potentiated diseases, belong in this category. The C/D concept predicts, other factors being equal, that the risk of initiation and progression of these diseases at all ages is directly related to the C/D ratio, individuals with elevated C/D ratios being at high risk.

Adrenal Cortex Hormones↗

PubMed1997

Direct radioimmunoassay of progesterone in saliva.

We have developed a simple, direct radioimmunoassay for progesterone in saliva. The correlation coefficient (r) between the direct assay and an extraction procedure was 0.92 (n = 65, P < 0.001), and the correlation between concurrent serum and salivary progesterone concentrations in the luteal phases of menstrual cycles of 48 women was 0.75 (P < 0.001). Whereas certain polystyrene and polyethylene vials and tubes were found to bind and remove up to 87% of the progesterone from saliva, other plastic and glass surfaces were satisfactory for the procedure. Intraassay and interassay CVs from values greater than 300 pmol/L were 12.0 and 12.4%, respectively. The assay sensitivity was 48 pmol/L. Collection of saliva is a more convenient and less invasive technique for frequent sample collection than phlebotomy, and is useful for monitoring ovulation and assessment of luteal function in women clinically.

Adult↗

PubMed1997

Hormonal responses to psychological stress in men preparing for skydiving.

The purpose of the study was to examine the relationship between the hormonal and psychological responses of young men about to engage in a potentially life-threatening event. Subjects were recruited to take their first skydiving jump. The scores on questionnaires designed to assess anxiety were not significantly increased at 0800 h on the morning before the jump by comparison with scores obtained from the same subjects 3-5 days previously. However, a psychological instrument for rating of events indicated significantly increased intensity, and sympathetic nervous system activity, as measured by the salivary amylase response, was increased over self-control values. Salivary cortisol and testosterone levels were significantly lower on the morning of the jump than self-control values and values in control subjects determined at the same time of day. However, plasma LH was not suppressed. The anxiety and stress measures as well as the rating of events rose to high levels just before the jump. With the exception of testosterone, which remained low, serum cortisol, PRL, and GH all increased greatly subsequent to the rise in psychological measures, reached peak values before or shortly after landing, and declined significantly within the next hour. Anxiety and subjective stress scores declined to those of the self-control values within 15 min after landing, but the rating of events scale remained significantly elevated. In summary, reported anxiety associated with a purely psychological stressor was suppressed until within a few hours preceding the event, but was preceded by an increase in sympathetic nervous system activity and suppression of plasma cortisol and salivary testosterone levels. The event itself was associated with a reversal of the cortisol decline; other stress-associated hormones increased, but salivary testosterone remained low.

Adult↗

PubMed1996

Disappearance and unexpected reappearance of progesterone in the circulation of the monkey: novel hormone kinetics.

1. Intravenous injection of [3H]progesterone in non-pregnant monkeys resulted in total disappearance of the labelled hormone from the circulation within 3 h. However, 0.5-1.75 h after disappearance the hormone reappeared, reaching 20% (median, 5%) of the initial maximal concentration. 2. Reappearance of labelled hormone was accompanied by similar fluctuations in the levels of labelled metabolites, [3H]20 alpha-dihydroprogesterone and [3H]17 alpha-hydroxyprogesterone, which reached 61% (median, 14%) and 120% (median, 13%), respectively, of the initial maximal concentrations. 3. Chromatography was used to separate labelled progesterone and its metabolites. Efficiency of the procedure was determined separately in each sample and for each steroid. All data were corrected for percentage recovery. 4. Analytical equations were devised, based on the theory of compartmental systems with continuously distributed time lags, to describe the unexpected kinetics of progesterone levels. The coefficients of determination ranged from 86 to 99% (median, 96%) which indicates that the equations enabled reliable prediction of hormone levels in blood within the time range studied. 5. The unexpected reappearance of labelled progesterone cannot be explained by hormone secretion but only by a delayed release from tissue stores, since progesterone does not undergo enterohepatic recirculation. Thus, a previously undescribed mechanism affecting circulating progesterone levels, and perhaps those of other hormones, exists.

17-alpha-Hydroxyprogesterone↗

PubMed1996

Longitudinal study of adrenal steroids in a cohort of HIV-infected patients with hemophilia.

The objective of the study was to relate plasma dehydroepiandrosterone sulfate (DHEA-S) concentrations to the progression of HIV infection in individual HIV-infected men with hemophilia and to obtain information on the cause of DH EA-S alterations. Blood samples were obtained from 16 men with hemophilia; in 9 men serial samples were available for up to 11 years after HIV-1 infection. Control samples were obtained from men of comparable ages without hemophilia or HIV infection. Measurements were made of CD4+ cell counts, plasma adrenocorticotropic hormone (ACTH), cortisol, DHEA, DHEA-S, and prolactin. Before HIV infection, men with hemophilia had significantly lower plasma levels of DHEA-S than control men. After infection, 3 of 9 subjects studied serially had little or no change in plasma DHEA-S levels or in CD4+ cell counts over 11 years. Four of the 9 i n whom AIDS developed had progressive decreases in plasma DHEA-S concentrations that, in some cases, preceded a precipitous fall in CD4+ cell counts. Major decreases in plasma DHEA-S levels before falls in CD4+ counts were observed in 2 ot her subjects who had other severe illnesses. None of the decreases in DHEA-S levels were associated with decreased concentrations of plasma cortisol, ACTH, or prolactin. We conclude that plasma DHEA-S is an indicator of general health rather than a specific indicator for progression of HIV. The decrease in plasma DHEA-S is not related to ACTH stimulation of the adrenal gland or to cortisol secretion, but it may be related to cytokines that can inhibit 17-hydroxylation of DH EA-S precursors.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Salivary alpha-amylase as a measure of endogenous adrenergic activity.

This investigation was designed to evaluate the production rates and concentrations of salivary alpha-amylase as a measure of adrenergic activity under several conditions of stress in human subjects. Saliva and blood samples were simultaneously collected from men at four 15 min intervals both before and after regimens for exercise, a written examination, or a rest period. The regressions of salivary alpha-amylase on plasma norepinephrine (NE) concentrations were significant for both exercise (P < 0.001) and examination (P < 0.01) protocols. Aerobic exercise induced a 3-fold mean increase in alpha-amylase; both NE and epinephrine (EP) increased approximately 5-fold over control levels. Levels of alpha-amylase and NE returned to control levels within 30-45 min after exercise, but EP remained elevated by approximately 2-fold during the remaining hour of observation. During the written examination, alpha-amylase and NE, but not EP, concentrations increased in parallel. In further studies the effects of exercise and exposure to heat and cold on the relationship of salivary alpha-amylase to heart rate and body temperature were investigated. Greater intensities of exercise were associated with greater increases in alpha-amylase concentrations. During heat exposure in a sauna (66 degrees C for 40 min) amylase, heart rate and body temperature all increased progressively. However, during exposure to cold (4 degrees C for 40 min) amylase increased rapidly, though heart rate and body temperature remained unchanged. Salivary cortisol concentrations were unchanged during exposure to heat or cold. We conclude that salivary alpha-amylase concentrations are predictive of plasma catecholamine levels, particularly NE, under a variety of stressful conditions, and may be a more direct and simple end point of catecholamine activity than are changes in heart rate.

Chromatography, High Pressure Liquid↗

PubMed1996

The effect of sequential and simultaneous breast pumping on milk volume and prolactin levels: a pilot study.

Mothers who must express milk for a prolonged period frequently report that milk volumes decrease. The purpose of this pilot study was to assess the feasibility of having a sample of lactating mothers of preterm infants follow a specific breast pumping protocol, express milk mechanically for six weeks, and have a subsample consent to venipuncture. This pilot study compared the effects of pumping breasts sequentially or simultaneously on milk volume and prolactin levels in mothers of preterm infants. Nine lactating mothers were randomly assigned to a sequential single or simultaneous double electric breast pumping system. Prolactin levels were examined in four mothers on days 21 and 42 postpartum. The sequential single and simultaneous double groups had mean baseline prolactin levels of 50.8 ng/ml and 40.6 ng/ml, respectively on day 21, and 26.6 ng/ml and 34.5 ng/ml, respectively, on day 42 postpartum. At 9 and 12 weeks postpartum mothers were queried about their lactational status. The results suggested that milk yield may be maintained or increased with frequent use of the simultaneous double pumping system. Further study is needed to confirm results of this pilot study.

Adult↗

PubMed1996

Neonatal androgenization potentiates the inhibitory effects of blood withdrawal on ovulation in the rat.

Rats treated on Day 5 of life with testosterone propionate (TP) were tested for their ovulatory response to pregnant mare's serum gonadotropin (PMSG) on the 30th day of life with and without cardiac puncture under ketamine/xylazine anesthesia. TP without cardiac puncture in doses of 0.625, 1.25, or 2.5 microg did not inhibit ovulation, but 5.0 microg of TP inhibited ovulation in 15 of 16 rats. When cardiac puncture was performed at 1900 hr in rats not given TP, seven of eight ovulated on Day 33. However, none of the rats that received either 1.25 or 2.5 microg of TP ovulated after cardiac puncture at 1900 hr, and only one of seven given the 0.625-microg dose ovulated. Thus, the stress of bleeding greatly enhanced the inhibitory effect of otherwise ineffective doses of TP. The preovulatory luteinizing hormone (LH) surge was delayed and diminished by neonatal TP in a dose-related manner in animals from which blood was drawn from a previously inserted catheter. When blood drawn from similarly TP-treated animals by cardiac puncture, serum levels of LH were further reduced. Progesterone, given at 1100 hr on Day 32, was capable of partially overcoming the inhibitory effects of the combined treatments on both ovulation and serum LH levels at all but the highest dose of TP tested (5.0 microg). We conclude that neonatal exposure to androgen sensitizes rats to ovulation-inhibiting factors, such as bleeding, in a manner which appears to delay as well as inhibit the preovulatory release of LH. Such early exposure to androgen, therefore, may determine the susceptibility of individuals to reproductive failure in adult life.

Animals↗

PubMed1995

Estrogenic and antiestrogenic activities of anordiol: a comparison of uterine and vaginal responses with those of clomiphene citrate.

Anordiol (2 alpha,17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta,17 beta-diol) has been variously characterized as an estrogen and as an antiestrogen. To more completely understand the pharmacological properties of this contraceptive steroid, simultaneous responses were studied in uterine, vaginal, and hepatic tissues. Rats received 4 daily sc injections with either anordiol, clomiphene citrate (CC), or the vehicle alone (C+) starting on the first day of pseudopregnancy. Uteri were traumatized on day 4 of pseudopregnancy, and rats were sacrificed 5 days later. A pseudopregnant group without uterine trauma served as a negative control (C-). Mean uterine weights per animal and cytosolic estrogen (EcR) and progesterone (PcR) receptor activities per g of DNA were all 5- to 7-fold greater in the C+ group than in the other groups (all p < 0.05). However, anordiol and CC suppressed uterine weight without suppressing the stromal proliferative response; the DNA content of the uteri of anordiol- and CC-treated rats was similar to that of C+ rats. Vaginal tissue exhibited estrogenic responses to anordiol and CC with an increase in epithelial stratification compared to the C+ and C- groups even though no difference in levels of EcR/g of DNA were expressed 5 days after the last antiestrogen dose. Binding affinities and serum E2 and progesterone (P) concentrations were not statistically different among the groups. In conclusion, anordiol produced responses in the uterus and vagina of the pseudopregnant rat which were indistinguishable from those of CC, and, therefore, we conclude that anordiol acts on these tissues as an antiestrogen.

Animals↗

PubMed1995

Hormonal and pregnancy relationships to rheumatoid arthritis: convergent effects with immunologic and microvascular systems.

OBJECTIVE: To review sex hormones and rheumatoid arthritis (RA) and the interrelationships between hormonal, immunological, and vascular systems. DATA SOURCES: Publications detailing serum sex hormone levels and their HLA interactions, steroidogenesis, pregnancy, and therapeutic uses of sex hormones in RA. STUDY SELECTION: Controlled studies of sex hormone levels in RA patients not previously treated with glucocorticoids. DATA EXTRACTION: Mean (+/- SD) serum levels of dehydroepiandrosterone sulfate (DHEAS), testosterone (T), and estradiol (E2). DATA SYNTHESIS: Mean (+/- SD) levels were collated into tables for women with pre-versus postmenopausal onsets of disease and men. Data were also ordered across all study groups by increasing mean levels of the control subjects. Pooled data were summarized statistically, and major sources of variation between the studies were identified. CONCLUSIONS: Serum DHEAS, an adrenal androgen, was impressively decreased among women with premenopausal onset of RA. One study showed such deficiency years before disease onset. Serum T was somewhat decreased in the premenopausal onset group, but could be explained by decreased peripheral conversion of the lower levels of adrenal androgens. Women with postmenopausal onset of RA had modestly decreased serum DHEAS levels overall, but no difference in serum T, compared with controls. Male RA cases had consistently decreased serum levels of T, but not of DHEAS. Serum E2 was comparable in all RA versus control groups. The complex biology of pregnancy was interpreted as an example of vital interactions between hormonal, immunological, and vascular systems, as they may relate to the physiopathology of RA. The major age, sex, and hereditable determinants of RA were compared within a composite table of estimated relative risks. Elucidation of the interacting risk factors offers promising avenues of research in this complex disease.

Adrenal Cortex Hormones↗

PubMed1995

Effect of endurance exercise on ovulation in the rat.

This study was designed to evaluate individual variation in ovarian responses to exercise. Rats ran on a treadmill (15% incline) at a rate of 26 m.min-1 for 90 min every day for 14-21 d; control rats were placed on a stationary treadmill for the same period of time. Based on daily vaginal cytology, 9 of 17 exercising rats had abnormal ( > 5 d) estrous cycles in the first cycle of training compared to only 2 of 19 controls. Throughout the training period, the length of estrous cycles of 8 of the 17 exercising rats were relatively unaffected; the mean length of completed cycles was 5.1% +/- 0.4 (SE) d. However, of those length of completed cycles was 5.1 +/- 0>4 (SE) d. However, of those thought to have ovulated based on vaginal cytology, fewer exercising than control rats had new corpora lutea on their ovaries. In exercising rats acyclic periods of up to 21 d were associated with serum progesterone levels similar to those of the diestrus phase of the estrous cycle (mean, 29 +/- 4 SE nmol.l-1). We conclude that treadmill running extends the period of progesterone secretion, delaying ovulation in a susceptible population of rats, and that vaginal cornification may not be an accurate indication of ovulation in these animals.

Animals↗

PubMed1994

Effect of anordiol on ovarian hormone secretion, ovulation, and uterine and vaginal responses in the immature rat.

The purpose of this investigation was to determine the estrogenic and antiestrogenic activities of the potential contraceptive agent anordiol in the immature rat. A dose of 2.45 mumol of anordiol (AD), estradiol (E2), clomiphene citrate (CC), tamoxifen (TA), or the vehicle alone was administered to rats on the 25th and 29th days of age. Serum hormones were measured between 16:00 and 17:00 on days 30, 31, and 32; organ weights were determined on day 32. Anordiol and estradiol treatments significantly increased ovarian and uterine weight and serum LH concentrations, but CC and TA had no effect on these parameters. Vaginal cornification occurred before day 32 in all rats receiving anordiol or estradiol and in 3/5 and 4/5 rats receiving CC and TA, respectively, but not in control rats. Based on serum progesterone levels, ovulation was induced only in rats receiving anordiol or estradiol. All of the compounds tested significantly increased serum testosterone above levels in control animals, but both AD and E2 induced ovulation without a further increase in serum testosterone. We conclude that in the immature rat anordiol produces estrogenic responses in the vagina, uterus and in the hypothalamic-pituitary-ovarian axis, whereas TA and CC are estrogenic only on the vaginal and uterine epithelium.

Animals↗

PubMed1994

Pharmacokinetics and pharmacodynamics of anordrin (2 alpha, 17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta, 17 beta-diol diproprionate).

In order to determine the pharmacokinetics of anordrin a dose of 0.2 mg/kg of [3-14 C]anordrin was administered i.v. to 5 cynomolgus monkeys; the same monkeys received the same dose i.m. at a later date. An additional 3 monkeys received 1.0 mg/kg of [3-14C]anordrin i.m. After administration of the compound, the dipropionate esters of anordrin were rapidly hydrolyzed to the dihydroxy parent compound, anordiol. After i.v. administration, anordrin had a mean residence time (MRT) of 5.0 +/- 1.3 (SE) min. [14C]Anordiol formed from [14C]anordrin had an MRT of 139 +/- 27 (SE) min. The metabolic clearance rates (MCR) of anordrin and anordiol were 55 and 34 mL/min.kg, respectively. The apparent volume of distribution at steady state (Vss) for anordrin was 276 mL/kg, 7.5% of body weight of the animals; anordrol had a much larger Vss of 4460 mL/kg. The MRT of anordiol after i.m. administration of 1.0 mg/kg of [14C]anordrin was 26.3 days. An average of 44% of the dose appeared in urine regardless of the route of administration or dose. The MRT values of total radioactivity were the same when calculated from serum or urine after an i.v. dose, but after i.m. administration, values from urine were approximately 60% of that calculated from serum, indicating that products appearing in urine had a shorter MRT than products appearing primarily in feces. A separate group of monkeys was given anordrin i.m. in doses ranging from 0.1 to 0.4 mg/kg on the first day of menses. The regression of length of menstrual cycle on dose was significant (P = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

The response of the growth hormone and insulin-like growth factor I axis to medical castration in women with polycystic ovarian syndrome.

OBJECTIVE: To assess the impact of ovarian hormone deprivation on serum concentrations of GH and insulin-like growth factor I (IGF-I) in women with polycystic ovarian syndrome (PCOS). DESIGN: Growth hormone and IGF-I levels were measured before, during, and at the end of a 6-month period of treatment with leuprolide acetate (LA) depot. Normal cycling and ovariectomized women served as controls. SETTING: The Clinical Research Center of Northwestern University Medical School. PATIENTS: Six women with PCOS, seven normal cycling women, and six ovariectomized women. INTERVENTIONS: The PCOS and normal cycling subjects were treated with six consecutive monthly injections of LA depot 3.75 mg IM. MAIN OUTCOME MEASURES: Circulating concentrations of GH and IGF-I. RESULTS: After 3 months of treatment, GH levels decreased modestly in the PCOS group; however, these changes were not significant. No further decline was observed at 6 months. Growth hormone levels were unaffected in the normal cycling group. Levels of IGF-I remained unchanged in both groups. Mean baseline levels of both GH and IGF-I in the ovariectomized group were lower than those of the normal cycling and PCOS groups at all time points, but not significantly so. CONCLUSIONS: Medical castration fails to significantly alter serum GH and IGF-I levels in either normal cycling or women with PCOS. These data indicate that GH secretion is not modulated by hormones of ovarian origin in either group, at least over the period of time studied.

Adult↗

PubMed1994

Successive time courses of strength development and steroid hormone responses to heavy-resistance training.

Subjects (5 males, 5 females) performed heavy-resistance exercise at a constant stimulus 3 days/wk for 8 wk. Work rates were then increased to higher but constant levels for an additional 8 wk. Half times of the first training period were 14 and 10 days for the bench press and parallel squat, respectively. The second time course resulted in only one-third of the overall magnitude of strength increases for both exercises as the first, and the kinetics were slower in the parallel squat but similar in the bench press (half time 13 days). Skeletal muscle fiber area was significantly increased (19%) in fast-twitch fibers by the end of the second training period. Postexercise elevations in serum cortisol and prolactin were seen only in the male subjects. Because the males trained at considerably higher work loads than the females, these results imply that absolute amounts of resistance may be an essential requirement for inducing certain hormonal responses. Serum cortisol levels in males after exercise were blunted by the 5th wk of the first time course. For serum testosterone, neither resting nor higher post-exercise concentrations were different at any point of the training periods for either sex. We conclude that the strength time course results are not inconsistent with current thought on factors contributing to strength accumulation. The absence of a specific serum androgenic response with strength development may be related to the fact that the constant exercise stimulus is not conducive to establishing clear-cut hormone-strength relationships.

Adult↗

PubMed1993

Effects of the antiestrogen anordiol on ovulation and endometrial histology in the rat.

The rat was evaluated as a model for the study of the folliculostatic properties of anordiol (2 alpha,17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta,17 beta-diol) which have been previously demonstrated in the primate. The effects in the rat were similar to those in the monkey in that anordiol: 1) extended the period of time for ovulation to occur, and 2) was effective only when administered during the early preantral stage of follicular development. The effect was different in that anordiol resulted in more complete luteolysis of newly formed corpora lutea. The presence of cornified cells in the vaginal smears 2 days after treatment with anordiol was a result of luteolysis and an intrinsic estrogenic activity of anordiol. Ovulation occurred on the first estrus after treatment whether the animals received 13 treatments every 5 days or only a single dose of anordiol. The uterine responses were characteristic of an antiestrogenic action of anordiol. It is concluded that the rat is a reasonable model for studies of the mechanism(s) of action of anordiol.

Animals↗

PubMed1993

Effects of subchronic implantation of hydrocortisone phosphate-releasing osmotic pumps on peripheral gonadotropin levels and estradiol feedback to gonadotropin secretion in the cynomolgus monkey.

The purpose of our study was to investigate subchronic effects of moderate hypercortisolemia on serum gonadotropin and estradiol (E2) levels in the primate using a repeated-measures experimental design. Osmotic pumps which released hydrocortisone 21-phosphate (HP) at a dose of 5 mg/day were implanted subcutaneously (s.c.) in each of five 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 hormone infusion. Subsequently, osmotic pumps which released HP at a higher dose of 15 mg/day were implanted s.c. in four of the initial five monkeys for the longer period of two menstrual cycles. The pumps were filled with saline for the two additional control cycles, one of which preceded and one of which followed HP infusion at 15 mg/day. The control cycle which followed HP infusion at 5 mg/day and the control cycle which preceded HP infusion at 15 mg/day were separated by at least one menstrual cycle. Administration of HP at the lower dose elevated serum cortisol levels 1.4-fold and decreased serum adrenal androgens to 0.6 of the pretreatment baseline. The higher dose of HP elevated serum cortisol levels 1.7-fold and suppressed serum adrenal androgens to 0.4 of the baseline. In the menstrual cycle following HP infusion serum cortisol levels were depressed to 0.8 and 0.6 of the pretreatment levels after the lower and the higher dose of HP, respectively. Serum levels of adrenal androgens returned to the baseline after the lower dose of HP, but were still suppressed to 0.5 of the baseline after the higher treatment dose. Implantation of pumps which released 5 mg/day of HP did not affect gonadotropin levels in the serum, either in the follicular phase (FP) or the luteal phase (LP) of the menstrual cycle. Serum E2 levels were increased by 77% in the FP during HP infusion at 5 mg/day (p < 0.001), but returned to control values in the LP. Implantation of pumps which released 15 mg/day of HP raised serum luteinizing hormone (LH) levels throughout the two menstrual cycles of treatment, by 111 and 96% in FPs (p < 0.001), and by 84 and 70% in LPs (p < 0.001). Conversely, serum follicle-stimulating hormone (FSH) levels were decreased by 45 and 50% in FPs (p < 0.05), and by 54 and 50% in LPs (p < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Glands↗

PubMed1993

The impact of subchronic hypercortisolemia on progesterone metabolism and the luteinizing hormone-progesterone axis in the cynomolgus monkey.

The purpose of the study was to assess the impact of subchronic hypercortisolemia on progesterone (P) metabolism and production and on peripheral LH levels in a nonhuman primate using a repeated measures experimental design. Osmotic pumps that released hydrocortisone phosphate (HP) at a dose of 15 mg/day were implanted sc in seven cynomolgus monkeys for two menstrual cycles. The pumps were filled with saline for the two control cycles, which either preceded (three animals) or followed (four animals) HP infusion. P metabolism, P production, and episodic secretion of LH were determined 8 +/- 1 days after the serum estradiol peak in the second control cycle and in the second cycle of HP infusion in each monkey, after iv bolus administration of 50 microCi [3H]P, followed by a 6-h blood sampling period. HP infusion elevated serum cortisol levels 1.6-fold. Serum P levels were decreased throughout the luteal phase by 58% (P < 0.01). The MCR of P and the volume of distribution at steady state of P were increased by 200% during HP infusion (both P < 0.005). The production rate of P was increased by HP treatment in five of seven monkeys. HP infusion increased the ratio of 20 alpha-[3H]dihydroprogesterone to [3H]P in serum from 0.5 to 1.0 (P < 0.05) while decreasing the fraction of [3H]P and its metabolites excreted in urine from 20% to 11% (P < 0.05). Serum LH levels, determined over a 5.25-h period in the luteal phase, were elevated by 200% during HP treatment (P < 0.05). Episodic secretion of LH during treatment was characterized by a 660% increase in the pulse amplitude (P < 0.05) and an apparent decrease in the pulse frequency. The results of this study provide evidence that moderate elevation of serum cortisol levels for two menstrual cycles in primates 1) increases the MCR of P, which may be the cause of the observed decrease in serum P levels; and 2) elevates serum LH levels by amplifying its pulse amplitude, which may result in a compensatory rise in the production rate of P.

Animals↗