Differential sex steroid negative feedback regulation of pulsatile follicle-stimulating hormone secretion in healthy older men

Deconvolution analysis and steady-state sex-steroid hormone infusions in frequently sampled healthy older individuals

Johannes D. Veldhuis, Ali Iranmanesh, Eugeniusz Samojlik, Randall Urban

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The healthy aging male reproductive axis tends to exhibit a progressive decline in serum concentrations of biologically available testosterone with gradual concomitant reciprocal increases in both LH and FSH concentrations. However, relatively little is known about the sex steroid-mediated negative feedback regulation of physiologically pulsatile gonadotropin release in general, and episodic FSH release in particular, in older males. To examine the steroid hormone negative feedback control of pulsatile FSH secretion in healthy older men, we applied multiparameter deconvolution analysis to serum FSH (immunoradiometric assay) profiles obtained by sampling every 10 min over 24 h during steady state (4.5-day) infusions of estradiol (E2; 48 μg/day), 5α-dihydrotestosterone (DHT; 7.0 mg/day), or 5% dextrose in water in five healthy older men, aged 60-73 yr. We observed the following principal responses: 1) both E2 and DHT significantly suppressed mean and 24-h integrated serum FSH concentrations (P < 0.032); 2) the calculated daily secretion rate of FSH fell significantly in all five individuals during DHT infusion; 3) the apparent half-life of FSH decreased during E2 (but not DHT) infusion; 4) DHT infusion reduced the mass and frequency of FSH secretory bursts significantly; 5) neither E2 nor DHT treatment significantly attenuated the release of FSH stimulated by consecutive iv injections of GnRH (10 and 100 μg); and 6) integrated 24-h serum LH (immunoradiometric assay) concentrations decreased significantly during both DHT and E2 infusions, whereas mean LH release after the serial GnRH injections was not altered. Compared to younger men studied earlier in an identical fashion, older men had significantly reduced FSH intersecretory burst intervals, reflecting a higher FSH pulse frequency at baseline and during the steroid infusions and a significantly lower mass of FSH secreted per burst during E2 infusion. We conclude that healthy older men maintain intact negative feedback responsiveness of the hypothalamo-pituitary gonadotroph unit to exogenously delivered sex steroid hormones, and that individual sex steroid hormones differentially regulate specific features of pulsatile FSH release and half- life in older men.

Original languageEnglish (US)
Pages (from-to)1248-1254
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume82
Issue number4
DOIs
StatePublished - 1997

Fingerprint

Gonadal Steroid Hormones
Follicle Stimulating Hormone
Deconvolution
Steroids
Feedback
Gonadotropin-Releasing Hormone
Assays
Steroid hormones
Immunoradiometric Assay
Dihydrotestosterone
Serum
Gonadotropins
Feedback control
Half-Life
Testosterone
Estradiol
Aging of materials
Sampling
Gonadotrophs
Glucose

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{ffc3c2252144433caae68234d12bca95,
title = "Differential sex steroid negative feedback regulation of pulsatile follicle-stimulating hormone secretion in healthy older men: Deconvolution analysis and steady-state sex-steroid hormone infusions in frequently sampled healthy older individuals",
abstract = "The healthy aging male reproductive axis tends to exhibit a progressive decline in serum concentrations of biologically available testosterone with gradual concomitant reciprocal increases in both LH and FSH concentrations. However, relatively little is known about the sex steroid-mediated negative feedback regulation of physiologically pulsatile gonadotropin release in general, and episodic FSH release in particular, in older males. To examine the steroid hormone negative feedback control of pulsatile FSH secretion in healthy older men, we applied multiparameter deconvolution analysis to serum FSH (immunoradiometric assay) profiles obtained by sampling every 10 min over 24 h during steady state (4.5-day) infusions of estradiol (E2; 48 μg/day), 5α-dihydrotestosterone (DHT; 7.0 mg/day), or 5{\%} dextrose in water in five healthy older men, aged 60-73 yr. We observed the following principal responses: 1) both E2 and DHT significantly suppressed mean and 24-h integrated serum FSH concentrations (P < 0.032); 2) the calculated daily secretion rate of FSH fell significantly in all five individuals during DHT infusion; 3) the apparent half-life of FSH decreased during E2 (but not DHT) infusion; 4) DHT infusion reduced the mass and frequency of FSH secretory bursts significantly; 5) neither E2 nor DHT treatment significantly attenuated the release of FSH stimulated by consecutive iv injections of GnRH (10 and 100 μg); and 6) integrated 24-h serum LH (immunoradiometric assay) concentrations decreased significantly during both DHT and E2 infusions, whereas mean LH release after the serial GnRH injections was not altered. Compared to younger men studied earlier in an identical fashion, older men had significantly reduced FSH intersecretory burst intervals, reflecting a higher FSH pulse frequency at baseline and during the steroid infusions and a significantly lower mass of FSH secreted per burst during E2 infusion. We conclude that healthy older men maintain intact negative feedback responsiveness of the hypothalamo-pituitary gonadotroph unit to exogenously delivered sex steroid hormones, and that individual sex steroid hormones differentially regulate specific features of pulsatile FSH release and half- life in older men.",
author = "Veldhuis, {Johannes D.} and Ali Iranmanesh and Eugeniusz Samojlik and Randall Urban",
year = "1997",
doi = "10.1210/jc.82.4.1248",
language = "English (US)",
volume = "82",
pages = "1248--1254",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - Differential sex steroid negative feedback regulation of pulsatile follicle-stimulating hormone secretion in healthy older men

T2 - Deconvolution analysis and steady-state sex-steroid hormone infusions in frequently sampled healthy older individuals

AU - Veldhuis, Johannes D.

AU - Iranmanesh, Ali

AU - Samojlik, Eugeniusz

AU - Urban, Randall

PY - 1997

Y1 - 1997

N2 - The healthy aging male reproductive axis tends to exhibit a progressive decline in serum concentrations of biologically available testosterone with gradual concomitant reciprocal increases in both LH and FSH concentrations. However, relatively little is known about the sex steroid-mediated negative feedback regulation of physiologically pulsatile gonadotropin release in general, and episodic FSH release in particular, in older males. To examine the steroid hormone negative feedback control of pulsatile FSH secretion in healthy older men, we applied multiparameter deconvolution analysis to serum FSH (immunoradiometric assay) profiles obtained by sampling every 10 min over 24 h during steady state (4.5-day) infusions of estradiol (E2; 48 μg/day), 5α-dihydrotestosterone (DHT; 7.0 mg/day), or 5% dextrose in water in five healthy older men, aged 60-73 yr. We observed the following principal responses: 1) both E2 and DHT significantly suppressed mean and 24-h integrated serum FSH concentrations (P < 0.032); 2) the calculated daily secretion rate of FSH fell significantly in all five individuals during DHT infusion; 3) the apparent half-life of FSH decreased during E2 (but not DHT) infusion; 4) DHT infusion reduced the mass and frequency of FSH secretory bursts significantly; 5) neither E2 nor DHT treatment significantly attenuated the release of FSH stimulated by consecutive iv injections of GnRH (10 and 100 μg); and 6) integrated 24-h serum LH (immunoradiometric assay) concentrations decreased significantly during both DHT and E2 infusions, whereas mean LH release after the serial GnRH injections was not altered. Compared to younger men studied earlier in an identical fashion, older men had significantly reduced FSH intersecretory burst intervals, reflecting a higher FSH pulse frequency at baseline and during the steroid infusions and a significantly lower mass of FSH secreted per burst during E2 infusion. We conclude that healthy older men maintain intact negative feedback responsiveness of the hypothalamo-pituitary gonadotroph unit to exogenously delivered sex steroid hormones, and that individual sex steroid hormones differentially regulate specific features of pulsatile FSH release and half- life in older men.

AB - The healthy aging male reproductive axis tends to exhibit a progressive decline in serum concentrations of biologically available testosterone with gradual concomitant reciprocal increases in both LH and FSH concentrations. However, relatively little is known about the sex steroid-mediated negative feedback regulation of physiologically pulsatile gonadotropin release in general, and episodic FSH release in particular, in older males. To examine the steroid hormone negative feedback control of pulsatile FSH secretion in healthy older men, we applied multiparameter deconvolution analysis to serum FSH (immunoradiometric assay) profiles obtained by sampling every 10 min over 24 h during steady state (4.5-day) infusions of estradiol (E2; 48 μg/day), 5α-dihydrotestosterone (DHT; 7.0 mg/day), or 5% dextrose in water in five healthy older men, aged 60-73 yr. We observed the following principal responses: 1) both E2 and DHT significantly suppressed mean and 24-h integrated serum FSH concentrations (P < 0.032); 2) the calculated daily secretion rate of FSH fell significantly in all five individuals during DHT infusion; 3) the apparent half-life of FSH decreased during E2 (but not DHT) infusion; 4) DHT infusion reduced the mass and frequency of FSH secretory bursts significantly; 5) neither E2 nor DHT treatment significantly attenuated the release of FSH stimulated by consecutive iv injections of GnRH (10 and 100 μg); and 6) integrated 24-h serum LH (immunoradiometric assay) concentrations decreased significantly during both DHT and E2 infusions, whereas mean LH release after the serial GnRH injections was not altered. Compared to younger men studied earlier in an identical fashion, older men had significantly reduced FSH intersecretory burst intervals, reflecting a higher FSH pulse frequency at baseline and during the steroid infusions and a significantly lower mass of FSH secreted per burst during E2 infusion. We conclude that healthy older men maintain intact negative feedback responsiveness of the hypothalamo-pituitary gonadotroph unit to exogenously delivered sex steroid hormones, and that individual sex steroid hormones differentially regulate specific features of pulsatile FSH release and half- life in older men.

UR - http://www.scopus.com/inward/record.url?scp=0030904368&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030904368&partnerID=8YFLogxK

U2 - 10.1210/jc.82.4.1248

DO - 10.1210/jc.82.4.1248

M3 - Article

VL - 82

SP - 1248

EP - 1254

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 4

ER -