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Biomedical subjects

William S Evans

Publications and source records attributed to William S Evans.

10 recordsLinked to original sources
PubMed2006

Interictal and postictal circadian and ultradian luteinizing hormone secretion in men with temporal lobe epilepsy.

PURPOSE: Hypothalamic regulation of the reproductive axis in temporal lobe epilepsy (TLE), represented by the ultradian pulsatile secretion of luteinizing hormone (LH), has been shown to be altered interictally and postictally. Our objective is to determine if epilepsy or seizures disrupt normal circadian fluctuations of LH as well as circadian organization of ultradian bursts of LH. METHODS: We characterized LH secretion in 10 men with TLE during two 24-h blocks: an interictal epoch and a postictal epoch initiated by a seizure. Serum LH was measured every 10 min and characterized by circadian and ultradian patterns with cosinor and deconvolution analysis. RESULTS: Mean peak serum concentrations of LH occurred at approximately 0400 in controls, were significantly delayed approximately 5 h interictally, and were randomly distributed postictally. Burst amplitudes differed significantly by phase among controls, with the largest amplitudes between 0101 and 0700 and the smallest between 1301 and 1900. No phase differences were present in interictal or postictal epochs. Burst frequency weakly but significantly was slowest between 0101 and 0700 in controls, but did not differ significantly by phase in either interictal or postictal epochs. Postictal LH burst frequencies, but not amplitudes, were significantly decreased immediately postictally. CONCLUSION: The pulsatile secretion of LH in TLE is abnormal both in the circadian as well as the ultradian domain. Interictal effects consist mainly in loss of circadian fluctuations in LH burst amplitude, whereas postictal effects consist of altered burst timing. Altered daily patterns of neuroendocrine signals may underlie other disorders of homeostasis in TLE.

Activity Cycles↗
PubMed2005

Growth hormone response to graded exercise intensities is attenuated and the gender difference abolished in older adults.

We investigated the joint impact of age, gender, and exercise intensity on growth hormone (GH) secretion. At a university center, nine young men, eight young women, seven older men, and six older women were each tested on six randomly ordered occasions [control (C) and 5 exercise conditions (Ex)]. Serum GH concentrations were measured by immunochemiluminometry [10-min samples: 0700-0900 (baseline); 0900-1300 (C or Ex + recovery)]. Integrated GH concentrations (IGHC) were calculated by trapezoidal reconstruction, and GH secretion was modeled by deconvolution analyses. Subjects exercised from 0900 to 0930 at graded intensities [standardized to individual lactate threshold (LT)] of 25 and 75% of the difference between rest and LT, LT, and 25 and 75% of the difference between LT and peak oxygen consumption. Data were analyzed via mixed-effects ANOVA for repeated measures with post hoc contrasts. We found that 1) Ex elevated IGHC above C in all four cohorts, 2) 1.75 LT Ex resulted in maximal IGHC, 3) IGHC differed by gender in young (women > men) but not older adults, 4) older adults secreted 50% less GH during graded exercise, 5) Ex selectively augmented the mass of GH secreted per burst, and 6) higher Ex + recovery IGHC in young women was due to higher baseline IGHC, rather than greater stimulated GH secretion. We conclude that young women manifest a greater absolute and incremental IGHC response to exercise than postmenopausal women and men of any age. Age diminishes the GH response to exercise and abolishes the young-adult gender difference. Attenuation of GH responses to all exercise intensities in older adults has implications for exercise prescription because higher exercise intensities may be required to stimulate GH release in older adults.

Adult↗
PubMed2004

The effects of time following acute growth hormone administration on metabolic and power output measures during acute exercise.

We examined the effects of GH infusion on metabolism and performance measures during acute exercise. Nine males [(X+/-SEM): age 23.7+/-1.9 yr, height 182.6+/-1.6 cm, weight 77.3+/- 2.6 kg, percent fat 17.7+/-1.9%, peak oxygen consumption 37.9 +/- 2.9 ml/kg.min] completed six 30-min randomly assigned bicycle ergometer exercise trials at a power output midway between the lactate threshold and peak oxygen consumption. In five of the six trials, the subjects received a recombinant humanGHinfusion (10 microg/kg, 6-min square wave pulse) at 0800 h, followed by a 30-min exercise trial initiated at one of the following times: 0845, 0930, 1015, 1100, or 1145 h. During one of the six trials, the subject received a saline infusion followed by a 30-min exercise trial initiated at 0845 h. Mixed-effect, repeated-measures ANOVA analyses corrected for multiple comparisons revealed that there were no significant condition effects for total work, caloric expenditure, heart rate response, the blood lactate response, or ratings of perceived exertion response. However, acute GH administration resulted in a lower exercise oxygen consumption without a drop-off in power output. We conclude that the time of exercise initiation after GH infusion does not affect total work, caloric expenditure, heart rate response, blood lactate response, or ratings of perceived exertion but reduces oxygen consumption in response to 30 min of constant load exercise at an intensity above the lactate threshold. The last outcome may suggest that GH administration can improve exercise economy.

Adult↗
PubMed2004

Exaggerated 17-hydroxyprogesterone response to intravenous infusions of recombinant human LH in women with polycystic ovary syndrome.

Studies using pharmacological gonadotropin stimulation suggest that ovarian steroidogenesis is abnormal in the polycystic ovary syndrome (PCOS). We assessed ovarian steroid secretion in response to near-physiological gonadotropin stimuli in 12 ovulatory controls and 7 women with PCOS. A gonadotropin-releasing hormone-receptor antagonist (ganirelix, 2 mg sc) was given to block endogenous LH secretion, followed by dexamethasone (0.75 mg orally) to suppress adrenal androgen secretion. After ganirelix injection (12 h), intravenous infusions of recombinant human LH (0, 10, 30, 100, and 300 IU; each over 8 min) were administered at 4-h intervals in a pseudorandomized (highest dose last) manner. Plasma LH, 17-hydroxyprogesterone (17-OHP), androstenedione, and testosterone were measured concurrently. LH dose-steroid response relationships (mean sex-steroid concentration vs. mean LH concentration over 4 h postinfusion) were examined for each subject. Linear regression of 17-OHP on LH yielded a higher (mean +/- SE) slope in PCOS (0.028 +/- 0.010 vs. 0.005 +/- 0.005, P < 0.05), whereas extrapolated 17-OHP at zero LH was similar. The slopes of other regressions did not differ from zero in either PCOS or controls. We conclude that near-physiological LH stimulation drives heightened 17-OHP secretion in patients with PCOS, suggesting abnormalities of early steps of ovarian steroidogenesis. With the exception of 17-OHP response in PCOS, no acute LH dose-ovarian steroid responses were observed in controls or PCOS. Defining the precise mechanistic basis of heightened precursor responsiveness to LH in PCOS will require further clinical investigation.

17-alpha-Hydroxyprogesterone↗
PubMed2004

Short-term testosterone supplementation relieves growth hormone autonegative feedback in men.

The present study tests the postulate that testosterone (Te) stimulates GH secretion, in part, by attenuating autonegative feedback. To this end, 13 healthy men (ages 43-71 yr) received three consecutive weekly im injections of placebo (Pl) (n = 7) or Te (200 mg) (n = 6) in a prospectively randomized, double-blind, parallel-cohort design. An iv pulse of saline or recombinant human (rh)GH (3 micro g/kg.6 min) was infused 2 h before bolus saline or GH-releasing peptide (GHRP)-2 (1 micro g/kg) in the fasting state. Blood was withdrawn every 10 min, GH concentrations were quantitated by chemiluminometry, secretion was determined by deconvolution analysis, and outcomes were compared by ANOVA. After Pl, rhGH suppressed basal, pulsatile, and GHRP-2-stimulated GH secretion by 2.6-, 2.4-, and 2.1-fold, respectively (each P < 0.03), and truncated GHRP-2-stimulated GH secretory bursts (P < 0.005). Compared with Pl, Te: 1) stimulated basal and pulsatile GH secretion by 1.9 and 2.4-fold (P < 0.01 and P < 0.02), respectively; 2) reduced feedback on basal GH secretion (P < 0.01); 3) blunted GHRP-2-stimulation by 1.9-fold (P < 0.01); and 4) facilitated initial recovery of rhGH-suppressed GH concentrations (P < 0.005). The foregoing actions were selective, inasmuch as Te did not relieve autoinhibition of pulsatile GH secretion. In summary, short-term Te supplementation decreases rhGH-imposed negative feedback on basal GH secretion and enhances early escape of GH from autoinhibition. In principle, such actions could potentiate the renewal of high-amplitude pulses of GH in androgen-replete individuals.

Aged↗
PubMed2003

Control of LH secretory-burst frequency and interpulse-interval regularity in women.

Hypothalamic neurons generate discrete bursts of gonadotropin-releasing hormone (GnRH) and thereby pulses of luteinizing hormone (LH) at randomly timed intervals centered on a probabilistic mean frequency. We tested the hypothesis that physiological mechanisms govern not only the number but also the stochastic dispersion of the GnRH/LH pulse-renewal process in humans; for example, in young women in the early (EF) and late (LF) follicular and midluteal (ML) phases of the menstrual cycle (n = 18) and in postmenopausal individuals (PM, n = 16). To this end, we quantify stochastic interpulse variability by way of the order-independent, two-parameter Weibull renewal process (Keenan DM and Veldhuis J. Am J Physiol Regul Integr Comp Physiol 281: R1917-R1924, 2001) and the sequence-specific, model-free approximate-entropy statistic (ApEn) (Pincus SM. Proc Natl Acad Sci USA 88: 2297-2301, 1991). Statistical testing unveiled 1) reduced probabilistic mean LH secretory-burst frequency (lower lambda of the Weibull distribution) in ML compared with each of EF, LF, and PM (P < 0.001); 2) quantifiably more regular LH interburst-interval sets (elevated gamma of the Weibull density) in PM than in each of EF, LF, and ML (P < 0.01); 3) uniquely prolonged latency to maximal LH secretion within individual secretory bursts in ML (P < 0.01); and 4) comparably mean random, sequential LH interburst-interval and mass values (normalized ApEn) among the distinct hormonal milieus. From these data, we postulate that sex steroids and age determine daily LH secretory-burst number, quantifiable pulse-renewal variability, and secretory-waveform evolution.

Adolescent↗
PubMed2003

Estradiol supplementation enhances submaximal feed-forward drive of growth hormone (GH) secretion by recombinant human GH-releasing hormone-1,44-amide in a putatively somatostatin-withdrawn milieu.

To test the clinical hypothesis that an estrogen-enriched milieu enhances GHRH action, we administered placebo (Pl) and estradiol-17 beta (E(2)) orally for 23 d to six postmenopausal women in a prospectively randomized, double-masked, within-subject crossover design with 6 wk intervening. The GHRH stimulation protocol entailed consecutive i.v. infusion of L-arginine and a single i.v. pulse of saline or one of five randomly ordered doses of recombinant human GHRH-1,44-amide (0.03, 0.1, 0.3, 1.0, or 3.0 microg/kg) in a total of 12 separate morning, fasting sessions. GH secretion was monitored by sampling blood every 10 min for 6 h; chemiluminescence assay of GH concentrations; deconvolution analysis of stimulated GH release; and nonlinear dose-response reconstruction. Supplementation with E(2), compared with Pl: 1) increased (mean +/- SEM) E(2) concentrations from 18 +/- 3 (Pl) to 164 +/- 12 pg/ml (to convert to picomoles per liter, multiply by 3.57) (P < 0.001); 2) decreased IGF-I concentrations from 181 +/- 14 to 120 +/- 11 microg/liter (P < 0.01); 3) elevated mean GH concentrations from 0.27 +/- 0.06 to 0.59 +/- 0.08 microg/liter (P = 0.014); 4) potentiated GH secretion stimulated by L-arginine alone by 1.43-fold (P = 0.012); 5) reduced the ED(50) of GHRH from 0.27 +/- 0.02 to 0.13 +/- 0.01 microg/kg (P < 0.01), denoting enhanced GHRH potency; and 6) heightened the maximal slope of the dose-response function from 1.1 +/- 0.1 to 1.4 +/- 0.05 [( microg/liter) ( microg/kg)(-1)] (P < 0.05), signifying augmented pituitary sensitivity. The foregoing facilitative mechanisms were specific because E(2) replacement did alter maximal L-arginine/GHRH-induced GH secretion, indicating unchanged secretagogue efficacy. In conclusion, inasmuch as E(2) also attenuates inhibition of GH secretion by infused somatostatin and potentiates stimulation of GH secretion by GH-releasing peptide-2, we postulate that estrogenic steroids drive pulsatile GH production in part via mechanisms that include all three of GHRH, somatostatin, and putatively GH-releasing peptide/ghrelin signaling.

Aged↗
PubMed2002

Hypothalamic regulation of cyclic ovulation: evidence that the increase in gonadotropin-releasing hormone pulse frequency during the follicular phase reflects the gradual loss of the restraining effects of progesterone.

The luteal-follicular transition is characterized by decreasing plasma levels of E(2), progesterone (P), and inhibin A, with concomitant increases in FSH and LH levels. LH (and by inference GnRH) pulse frequency increases from 1 pulse every 3-4 h during the luteal phase to approximately 1 pulse/h at the midcycle LH surge. To examine the regulation of GnRH pulse frequency, we gave 10 normally cycling women transdermal E(2) and oral P to produce midluteal levels [364 +/- 65.0 pmol/liter (99 +/- 18 pg/ml) and 29.7 +/- 6.8 nmol/liter (9.3 +/- 2.1 ng/ml), respectively] for 10 d after the LH surge (d 0). P was then discontinued, and E(2) was given alone for 3 additional wk. Pulsatile LH secretion and follicular size were assessed on d 10, 17, 24, and 31. Results are presented as the mean +/- SEM. LH pulse frequency was 3.1 +/- 0.5 pulses/12 h after 10 d of E(2) and P, and remained low on d 17 when P had fallen below 1.6 nmol/liter (<0.5 ng/ml). In the continued presence of midluteal levels of E(2) [ approximately 360 pmol/liter (100 pg/ml)], LH pulse frequency increased on d 24 and 31 to 5.5 +/- 0.9 and 5.8 +/- 0.5 pulses/12 h, respectively, whereas pulse amplitude remained unchanged. FSH increased 2-fold, but follicular size did not change. These results are consistent with E(2) potentiating the effects of low concentrations of P on the GnRH pulse generator for at least 7 d, after which pulse frequency increases despite maintenance of E(2) levels. This supports the hypothesis that the increasing GnRH pulse frequency throughout the follicular phase reflects the gradual loss of the inhibitory actions of low concentrations of P.

Adult↗