Detection and characterization of peaks and estimation of instantaneous secretory rate for episodic pulsatile hormone secretion

Oerter, Karen E.; Guardabasso, Vincenzo; Rodbard, David

doi:10.1016/0010-4809(86)90014-5

Cited by 217 publications

(127 citation statements)

References 15 publications

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“…Time series of LH and FSH were first evaluated separately to estimate the random measurement error on the duplicates using the program PREDETEC.WK1 as previously described (19)(20)(21). Then secretory episodes on each time series were identified using the program DETECT as previously described (21) with a P value equal to 0.01 (1%) for the nominal falsepositive rate.…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic–pituitary–gonadal axis in two men with aromatase deficiency: evidence that circulating estrogens are required at the hypothalamic level for the integrity of gonadotropin negative feedback

et al. 2006

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Background: In men, the feedback of gonadotropins is regulated by estrogens that come from the aromatization of testosterone, but the relative contribution to the inhibition of LH and FSH secretion by the amount of locally produced estrogens within the hypothalamus and/or the pituitary, and the amount of circulating estrogens still remains unknown. Objective: In order to evaluate the effect of regulation induced by estradiol on the hypothalamicpituitary-gonadal (HPG) axis, we studied the pulsatility of LH and FSH in two aromatase-deficient men (called subject 1 and subject 2), in which the production rate of estrogen (both local and circulating) is completely, or at least severely, impaired. Design: FSH and LH were evaluated in terms of their pulsated secretion and as GnRH-stimulated secretion in two phases: phase 1, before estrogen treatment; and phase 2, during estrogen treatment with 25 mg transdermal estradiol twice weekly. Methods: Blood samples were taken during phase 1 and phase 2 at 0800 h for basal measurements of LH, FSH, inhibin B, testosterone, and estradiol. The analysis of the pulsatility of LH and FSH was performed by sampling every 10 min for 8 h in the two phases. Gonadotropin response to GnRH-stimulation test was studied by serial standard sampling after 100 mg GnRH i.v. bolus in phases 1 and 2. Results: Estrogen treatment led to a significant reduction in both LH-pulsated frequency (7.5G0.7 in phase 1, 4.5G0.7 in phase 2) and amplitudes (3.5G0.006 in phase 1, 1.9G0.4 in phase 2) of peaks, whereas FSH showed only a conspicuous reduction in serum levels and a trend towards the reduction of the amplitudes of its peaks without modification of the frequency of the pulses. Both testosterone and gonadotropins decreased during phase 2, whereas estradiol reached the normal range in both subjects. Transdermal estradiol treatment significantly lowered the peaks of both serum LH and FSH after GnRH as well as the incremental area under the curve after GnRH administration in both subjects. Basal serum inhibin B levels were slightly higher before transdermal estradiol treatment (phase 1) than during estrogen treatment (phase 2) in both subjects. Conclusions: The administration of estrogen to aromatase-deficient men discloses the effects of circulating estrogens on LH secretion, exerted both at pituitary level, as shown by the decrease of basal and GnRH-stimulated secretion of LH and the LH pulsed amplitude, and at hypothalamic level as shown by the reduction of the frequency of LH pulses. The present study, coupling the outcomes of basal, GnRH-stimulated and the pulsatile evaluation of LH and FSH secretion in two aromatase-deficient men, demonstrates that circulating estrogens play an inhibitory role in LH secretion by acting on the hypothalamus and the pituitary gland of men. The discrepancy among testosterone levels, the arrest of spermatogenesis and a slightly inappropriate respective increase of serum FSH (lower than expected) suggests a possible role of estrogens in the priming and the maturatio...

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Section: Discussionmentioning

confidence: 99%

Hypothalamic–pituitary–gonadal axis in two men with aromatase deficiency: evidence that circulating estrogens are required at the hypothalamic level for the integrity of gonadotropin negative feedback

et al. 2006

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“…Different approaches have been implemented ranging from discrete deconvolution (1,2,4,14,15), to parametric (3,16) and non-parametric deconvolution, (5)(6)(7)(8)17). As discussed earlier (8), the non-parametric approach is particularly well suited to the analysis of RTS (response-to-stimuli) hormone data.…”

Section: Discussionmentioning

confidence: 99%

“…As the direct formula to compute the serum concentration from the ISR is a convolution integral, the process of recovering the ISR from the observations is called deconvolution. In the past decade, deconvolution analysis of hormone data has been the subject of several studies (1)(2)(3)(4)(5). However, some of the parametric and discrete deconvolution techniques proposed in the literature were developed for the analysis of spontaneous secretion data and are not optimal to deal with the analysis of RTS data, for example those obtained in GnRH tests.…”

Section: Introductionmentioning

confidence: 99%

LH and FSH secretory responses to GnRH in normal individuals: a non-parametric deconvolution approach

Nicolao

Liberati²,

Veldhuis

et al. 1999

European Journal of Endocrinology

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Objective: To reconstruct the instantaneous secretion rate (ISR) of LH and FSH after GnRH administration in normal volunteers using non-parametric deconvolution, and to derive a direct integration formula to evaluate the amount of LH and FSH secreted during the first 60 min after the stimulus. Design and methods: First, the deconvolution method was validated in vivo by reconstructing doses ranging from 7.5 IU to 75 IU injected in three healthy adult volunteers whose endogenous LH had previously been downregulated by pretreating them, 3-4 weeks earlier, with 3.75 mg GnRH agonist i.m. Then, 40 healthy adult male volunteers were tested with a single 100 mg GnRH bolus, administered at 0 min. LH and FSH concentrations were determined at ¹30, 0, 15, 30, 45, 60, 90, and 120 min. Results and conclusions:The validation study, conducted over a 10-fold range of doses, demonstrated that non-parametric deconvolution provided a reasonably accurate estimate of the amount of hormone entering the circulation. Applying deconvolution to the LH and FSH responses to GnRH, the ISRs of both hormones were shown to have a similar pattern, with a clearly delimited pulse after the GnRH bolus. In conjunction with earlier analyses of estimates of GHRH-stimulated GH secretion, we conclude that secretagogues evoke discrete LH, FSH, and GH secretory bursts of about 60 min total duration, despite markedly unequal (glyco-)protein hormone half-lives (18-500 min). With respect to the assessment of total hormone release during the first 60 min after the stimulus, the integration formula provided a reliable approximation of the result obtained by deconvolution, and had a negligible dependence on the samples at times 90 and 120 min.

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“…Missing values comprised less than 0.5% of the total samples and were left blank. This method of pulse analysis has been compared in previous studies of normal women to the computerized peak detection program, Detect, version 4.8 (Oerter et al, 1986), and shown to provide similar estimates of pulse frequency (Nippoldt et al, 1989).…”

Section: Lh Pulse Analysismentioning

confidence: 99%

Pulsatile LH secretion in women with premenstrual syndrome (PMS): Evidence for normal neuroregulation of the menstrual cycle

Reame

Marshall

Kelch

1992

Psychoneuroendocrinology

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SUMMARYThe premenstrual syndrome (PMS) has been proposed to result from excessive exposure to and/or withdrawal of brain opioid activity during the luteal phase. Because hypothalamic opioids are believed to modulate GnRH secretion, in part under the influence of ovarian steroids, we performed longitudinal studies of gonadotropin and ovarian steroid secretion across ovulatory, symptomatic cycles of 17 PMS patients and 8 normal volunteers. Pulsatile LH secretion was measured every 10 min for 8 hr at times when central opioid activity was expected to be low (early follicular phase), high (mid-luteal phase; ML), and declining (late luteal phase). In both subject groups, a cycle-phase effect was observed for LH pulse frequency (p =<0.001) and amplitude (p =0.002), and for the transverse mean concentrations of LH (p =0.05), FSH (p <= 0.001), estradiol (E2) (p=<0.001) and progesterone (P) (p =<0.001). ML P secretion in PMS patients was pulsatile, and mean concentrations (over 30-60 min) were similar to those of normal controls. The changes in pulsatile LH secretion across the cycle were not different in the PMS patients compared to the normal women, though mean FSH in the ML phase was higher in the PMS group (p =<0.05). The similar changes in luteal LH pulse frequency fail to provide evidence that GnRH secretion is impaired, thus challenging the view that the neuroregulation of the menstrual cycle in women with PMS is markedly altered.

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Detection and characterization of peaks and estimation of instantaneous secretory rate for episodic pulsatile hormone secretion

Cited by 217 publications

References 15 publications

Hypothalamic–pituitary–gonadal axis in two men with aromatase deficiency: evidence that circulating estrogens are required at the hypothalamic level for the integrity of gonadotropin negative feedback

Hypothalamic–pituitary–gonadal axis in two men with aromatase deficiency: evidence that circulating estrogens are required at the hypothalamic level for the integrity of gonadotropin negative feedback

LH and FSH secretory responses to GnRH in normal individuals: a non-parametric deconvolution approach

Pulsatile LH secretion in women with premenstrual syndrome (PMS): Evidence for normal neuroregulation of the menstrual cycle

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