Strength-duration characteristics of estrogen effects on gonadotropin response to gonadotropin-releasing hormone in women. II. Effects of varying concentrations of estradiol
Young JR,Jaffe RB
Published March 1976The Journal of Clinical Endocrinology and Metabolism, 42(3), 432-442
Young, J. R., & Jaffe, R. B. (1976). Strength-duration characteristics of estrogen effects on gonadotropin response to gonadotropin-releasing hormone in women. II. Effects of varying concentrations of estradiol. The Journal of clinical endocrinology and metabolism, 42(3), 432-442. https://doi.org/10.1210/jcem-42-3-432
Young JR, Jaffe RB. Strength-duration characteristics of estrogen effects on gonadotropin response to gonadotropin-releasing hormone in women. II. Effects of varying concentrations of estradiol. J Clin Endocrinol Metab. 1976;42(3):432-442. doi:10.1210/jcem-42-3-432
Young, John R., and Robert B. Jaffe. "Strength-duration characteristics of estrogen effects on gonadotropin response to gonadotropin-releasing hormone in women. II. Effects of varying concentrations of estradiol." The Journal of clinical endocrinology and metabolism, vol. 42, no. 3, 1976, pp. 432-442.
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This study was designed to investigate the effect of varying concentrations of estradiol, administered to normal women, upon the gonadotropin response to synthetic gonadotropin-releasing hormone (GnRH or LRF). Beginning at 4 pm on the first day of the menstrual cycle, 19 studies were performed in subjects who received injections of estradiol benzoate (E2B every 12 h for 6 days). Concentrations of E2B administered (mug/kg/12 h) were: 0.3, 0.6, 1.25, 2.5, 3.75, and 5.0. Mean serum estradiol concentrations achieved at these respective concentrations of E2B were 43, 53, 91, 145, 195, and 305 pg/ml. Twelve h after the last E2B injection, an intravenous bolus of 100 mug GnRH was administered. Gonadotropin response to this dose of GnRH after E2B was compared with each subject's response in the early follicular phase of a previous (control) cycle during which no exogenous estradiol was administered.
To explore the pulsatile-release characteristics of LH and P in women with premenstrual syndrome (PMS) compared with age-matched phase-matched controls. Prospective, repeated measures, two-group study. Human volunteers in an academic research environment. Six women with rigorously defined prospectively determined PMS; six age-matched phase-matched controls. Frequency, amplitude, concentration, and coincident pulsatile release characteristics of LH and P at three symptom-related points of the luteal phase. No significant between-group differences in frequency, amplitude, or concentration were found. In pooled data, significant coincident pulsing between LH and P was demonstrated. The length of time between LH and P pulses systematically increased across the luteal phase, a finding not previously reported. In the PMS group only, significant coincident pulsing occurred at an unexpected zero time lag on the symptom-onset sampling day. A progressively increasing coupling interval may reflect the gradual decline of the corpus luteum. Presence of a zero time lag between LH and P at symptom onset in women with PMS may indicate an aberrance in corpus luteum response to LH stimulation.
It has become apparent in recent years that regulation of the ovulatory cycle cannot be accomplished solely through the mediation of the two pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Within the last decade, discoveries of additional regulatory mechanisms involved in the neuroendocrine control of the events of the ovulatory cycle have provided new insight into the control of this complex biological phenomenon (127). Among the most interesting of these discoveries are …
In rhesus monkeys with hypothalamic lesions (which appear to abolish the endogenous production of gonadotropin-releasing hormone), normal ovulatory mestrual cycles were reestablished by an unvarying, long-term replacement regimen consisting of one intravenous pulse of synthetic gonadotropic-releasing hormone per hour. This finding is in accord with the hypothesis that the pattern of pituitary gonadotropin secretion throughout the menstrual cycle (basal secretion interrupted, once every 28 days on the average, by a preovulatory surge) is not directed by alterations in hypothalamic gonadotropin-releasing hormone secretion but by the ebb and flow of ovarian estrogens acting directly on the pituitary gland.
Sims ST et al., 2021·BMJ open sport & exercise medicine·Free full text on PubMed Central
As the number of female athletes competing rises globally, training methodologies should reflect sex differences across critical metrics of adaptation to training. Surrogate markers of the autonomic nervous system (ANS) used for monitoring training load are heart rate variability (HRV) and resting heart rate (RHR). The aim was to investigate ovarian hormone effects on standard recovery metrics (HRV, RHR, respiratory rate (RR) and sleep duration) across a large population of female athletes. A retrospective study analysed 362 852 days of data representing 13 535 menstrual cycles (MC) from 4594 respondents (natural MC n=3870, BC n=455, progestin-only n=269) for relationships and/or differences between endogenous and exogenous ovarian hormones on ANS. HRV and return to baseline (recovery) decreased as resting HR and RR increased (p<0.001) from the early follicular to the late luteal phase of the MC. Patterning was paradoxical across phases for users of combined hormonal contraception (BC) as compared with the patterning of the MC. HRV and recovery start elevated and drop off quickly during the withdrawal bleed, rising through the active pill weeks (p<0.001). Progestin-only users had similar patterning as the MC. The relationship between normalised recovery and previous day strain is modulated by birth control type. BC exhibited steeper declines in recovery with additional strain-normalised recovery decreases by an additional 0.0055±0.00135 (p<0.001) per unit of strain; with no significant difference between MC and progestin-only (p=0.19). The patterning of ANS modulation from ovarian hormones is significantly different between naturally cycling women and those on BC, with the patterning dependent on the type of contraception used.
To examine the differential regulation of glycoprotein hormone secretion from the gonadotrope by GnRH, the Nal-Glu GnRH antagonist was administered to euthyroid women in the early follicular phase (days 1-5) of the menstrual cycle, and the results compared to previous studies with the Nal-Arg GnRH antagonist. After a 4-h period of baseline sampling at a frequency of every 10 min, a single sc dose of the GnRH antagonist was administered to each subject. Frequent sampling continued for 8 h, followed by hourly sampling for a further 16 h. LH, FSH, and free alpha-subunit were measured serially in assays with high specificity. There was a 90% concordance of LH and free alpha-subunit pulses during the baseline sampling period. Pulsatile secretion of LH and free alpha-subunit was immediately abolished at the highest dose of the Nal-Glu antagonist for at least 8 h. The maximum percent suppression of LH after administration of the Nal-Glu GnRH antagonist was 70 +/- 4%, 80 +/- 4%, and 83 +/- 1% at doses of 15, 50, and 150 micrograms/kg, respectively, compared to 51 +/- 10%, 70 +/- 5%, and 69 +/- 5% at doses of 50, 150, and 500 micrograms/kg Nal-Arg antagonist. Decreases in FSH were 28 +/- 2%, 32 +/- 7%, and 39 +/- 2%, with increasing doses of the Nal-Glu antagonist compared with 25 +/- 6%, 17 +/- 6%, and 28 +/- 4% reductions at increasing doses of the Nal-Arg antagonist. Free alpha-subunit decreased 22 +/- 4%, 23 +/- 4%, and 28 +/- 3% at increasing doses of the Nal-Glu antagonist and 12 +/- 4%, 27 +/- 4%, and 30 +/- 7% with increasing doses of the Nal-Arg antagonist. For the Nal-Glu antagonist, suppression of LH was greater than that of FSH and free alpha-subunit at all doses (P less than 0.001), while FSH suppression was greater than that of free alpha-subunit at the highest dose only (P less than 0.05). For the Nal-Arg antagonist, LH suppression was greater than that of FSH or free alpha-subunit at all doses (P greater than 0.01), and FSH suppression exceeded that of free alpha-subunit at the 50 micrograms/kg dose. Suppression of LH was greater with the Nal-Glu antagonist than with the Nal-Arg antagonist at doses of 50 and 150 micrograms/kg (P less than 0.05), and FSH suppression was greater with the Nal-Glu antagonist at 150 micrograms/kg (P less than 0.01), while the degrees of maximum suppression were similar for the two different GnRH antagonists for free alpha-subunit.(ABSTRACT TRUNCATED AT 400 WORDS)
The internal or circadian timing system is deeply integrated in female reproductive physiology. Considerable details of rheostatic timing function in the neuroendocrine control of pituitary hormone secretion, adenohypophyseal hormone gene expression and secretion, gonadal steroid hormone biosynthesis and secretion, ovulation, implantation, and parturition have been reported. The molecular clock, an autonomous feedback loop oscillator of interacting transcriptional regulators, dictates the timing and amplitude of gene expression in each tissue of the female hypothalamic-pituitary-gonadal (HPG) axis. Although multiple targets of the molecular clock have been identified, many associated with critical physiological functions in the HPG axis, the full extent of clock-driven gene expression and physiology in this critical system remains unknown. Environmental circadian disruption (ECD), the disturbance of temporal relationships within and between internal clocks (brain and periphery), and external timing cues (eg, light, nutrients, social cues) due to rotating/night shift work or transmeridian travel have been linked to reproductive dysfunction and subfertility. Moreover, ECD resulting from exposure to endocrine disrupting chemicals, environmental toxins, and/or irregular hormone levels during sexual development can also reduce fertility. Thus, perturbations that disturb clock function at the molecular, cellular or systemic level correlate with significant declines in female reproductive function. Here we briefly review the evidence for molecular clock function in each tissue of the female HPG axis (GnRH neuron, pituitary, uterus, oviduct, and ovary), describe the human epidemiological and animal data supporting the negative effects of ECD on fertility, and explore the potential for novel chronotherapeutics in women's health and fertility.
PMID 767352 767352 DOI 10.1210/jcem-42-3-432 10.1210/jcem-42-3-432 Young et al. 1976, Young 1976
Cite this article
Young, J. R., & Jaffe, R. B. (1976). Strength-duration characteristics of estrogen effects on gonadotropin response to gonadotropin-releasing hormone in women. II. Effects of varying concentrations of estradiol. The Journal of clinical endocrinology and metabolism, 42(3), 432-442. https://doi.org/10.1210/jcem-42-3-432
Young JR, Jaffe RB. Strength-duration characteristics of estrogen effects on gonadotropin response to gonadotropin-releasing hormone in women. II. Effects of varying concentrations of estradiol. J Clin Endocrinol Metab. 1976;42(3):432-442. doi:10.1210/jcem-42-3-432
Young, John R., and Robert B. Jaffe. "Strength-duration characteristics of estrogen effects on gonadotropin response to gonadotropin-releasing hormone in women. II. Effects of varying concentrations of estradiol." The Journal of clinical endocrinology and metabolism, vol. 42, no. 3, 1976, pp. 432-442.
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