Steroidal regulation of biologically active luteinizing hormone secretion in men and women

Johannes D Veldhuis, M. L. Dufa

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The biological activity of circulating luteinizing hormone (LH) molecules can be assessed with high sensitivity, specificity, and precision by the in-vitro rat interstitial (Leydig)-cell testosterone (RICT) bioassay. Compared to immunoreactive estimates of the LH content of plasma, the living Leydig-cell bioassay integrates the functional in-vitro potency of all circulating LH isoforms, while simultaneously reflecting the effects of otherwise potentially confounding in-vivo antagonists of LH action on steroidogenesis. Here, we review the pathophysiological regulation by steroid hormones of bioactive LH secretion and clearance in men and women. Our investigations and those in the available literature indicate that: (i) exogenous (non-aromatizable) 5-α-dihydrotestosterone infusion suppresses LH bioactivity, whereas blockade of the endogenous androgen receptor with flutamide increases secretion of biopotent LH in men; (ii) endogenous androgen excess due to a masculinizing testosterone-secreting adrenal tumour in a post-menopausal woman reversibly suppressed plasma LH bioactivity markedly; (iii) exogenous oestradiol infusion will reduce whereas the antioestrogen, tamoxifen HCl, can increase bioactive LH secretion in young men; (iv) the effect of anti-oestrogen is blunted in healthy older men; (v) endogenous hyperoestrogenism due to an adrenal oestrogen-secreting tumour in a middle-aged man with gynaecomastia profoundly but reversibly inhibited bioactive LH secretion; (vi) in post-menopausal women, exogenous oestrogen administration, whether oral (diethylstilbestrol), percutaneous (oestradiol), or intravaginal (oestradiolimpregnated silastic ring), exerts a temporally biphasic effect on basal bioactive LH secretion, i.e. acute suppression (within 24 h), subacute escape (at 5-10 days), and longer-term inhibition (30 days); (vii) during the normal menstrual cycle, bioactive LH secretion is pulsatile and both frequency and amplitude regulated; and (viii) oestrogen exposure can enhance gonadotrophin releasing hormone (GnRH)'s stimulatory action on biologically active LH secretion, resulting in so-called GnRH self-priming. Oestrogen's facilitative effects are achieved by a novel mechanism, in which oestrogen augments LH secretory burst mass and duration. Moreover, GnRH dose-LH secretory response studies show that oestrogen promotes an increase in GnRH efficacy (maximal effects) but not GnRH sensitivity (potency or half-maximally effective doses of GnRH). We conclude that steroid hormones are primary regulators of physiologically pulsatile bioactive LH secretion in healthy men and women. Moreover, steroids exert potent pathological effects on biologically active LH release in conditions of selective hyperandrogenism or hyperoestrogenism due to steroid-secreting adrenal or gonadal tumours.

Original languageEnglish (US)
Pages (from-to)84-96
Number of pages13
JournalHuman Reproduction
Volume8
Issue numberSUPPL. 2
StatePublished - 1993
Externally publishedYes

Fingerprint

Luteinizing Hormone
Gonadotropin-Releasing Hormone
Estrogens
Steroids
Leydig Cells
Biological Assay
Testosterone
Estradiol
Hormones
Flutamide
Hyperandrogenism
Diethylstilbestrol
Estrogen Receptor Modulators
Glandular and Epithelial Neoplasms
Dihydrotestosterone
Androgen Receptors
Tamoxifen
Menstrual Cycle
Androgens
Oral Administration

Keywords

  • Bioactive
  • Gonadotrophin
  • Human
  • Pituitary
  • Pulsatile

ASJC Scopus subject areas

  • Developmental Biology
  • Physiology
  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

Steroidal regulation of biologically active luteinizing hormone secretion in men and women. / Veldhuis, Johannes D; Dufa, M. L.

In: Human Reproduction, Vol. 8, No. SUPPL. 2, 1993, p. 84-96.

Research output: Contribution to journalArticle

Veldhuis, Johannes D ; Dufa, M. L. / Steroidal regulation of biologically active luteinizing hormone secretion in men and women. In: Human Reproduction. 1993 ; Vol. 8, No. SUPPL. 2. pp. 84-96.
@article{5ac51357458d41b5b51cde2e8031f469,
title = "Steroidal regulation of biologically active luteinizing hormone secretion in men and women",
abstract = "The biological activity of circulating luteinizing hormone (LH) molecules can be assessed with high sensitivity, specificity, and precision by the in-vitro rat interstitial (Leydig)-cell testosterone (RICT) bioassay. Compared to immunoreactive estimates of the LH content of plasma, the living Leydig-cell bioassay integrates the functional in-vitro potency of all circulating LH isoforms, while simultaneously reflecting the effects of otherwise potentially confounding in-vivo antagonists of LH action on steroidogenesis. Here, we review the pathophysiological regulation by steroid hormones of bioactive LH secretion and clearance in men and women. Our investigations and those in the available literature indicate that: (i) exogenous (non-aromatizable) 5-α-dihydrotestosterone infusion suppresses LH bioactivity, whereas blockade of the endogenous androgen receptor with flutamide increases secretion of biopotent LH in men; (ii) endogenous androgen excess due to a masculinizing testosterone-secreting adrenal tumour in a post-menopausal woman reversibly suppressed plasma LH bioactivity markedly; (iii) exogenous oestradiol infusion will reduce whereas the antioestrogen, tamoxifen HCl, can increase bioactive LH secretion in young men; (iv) the effect of anti-oestrogen is blunted in healthy older men; (v) endogenous hyperoestrogenism due to an adrenal oestrogen-secreting tumour in a middle-aged man with gynaecomastia profoundly but reversibly inhibited bioactive LH secretion; (vi) in post-menopausal women, exogenous oestrogen administration, whether oral (diethylstilbestrol), percutaneous (oestradiol), or intravaginal (oestradiolimpregnated silastic ring), exerts a temporally biphasic effect on basal bioactive LH secretion, i.e. acute suppression (within 24 h), subacute escape (at 5-10 days), and longer-term inhibition (30 days); (vii) during the normal menstrual cycle, bioactive LH secretion is pulsatile and both frequency and amplitude regulated; and (viii) oestrogen exposure can enhance gonadotrophin releasing hormone (GnRH)'s stimulatory action on biologically active LH secretion, resulting in so-called GnRH self-priming. Oestrogen's facilitative effects are achieved by a novel mechanism, in which oestrogen augments LH secretory burst mass and duration. Moreover, GnRH dose-LH secretory response studies show that oestrogen promotes an increase in GnRH efficacy (maximal effects) but not GnRH sensitivity (potency or half-maximally effective doses of GnRH). We conclude that steroid hormones are primary regulators of physiologically pulsatile bioactive LH secretion in healthy men and women. Moreover, steroids exert potent pathological effects on biologically active LH release in conditions of selective hyperandrogenism or hyperoestrogenism due to steroid-secreting adrenal or gonadal tumours.",
keywords = "Bioactive, Gonadotrophin, Human, Pituitary, Pulsatile",
author = "Veldhuis, {Johannes D} and Dufa, {M. L.}",
year = "1993",
language = "English (US)",
volume = "8",
pages = "84--96",
journal = "Human Reproduction",
issn = "0268-1161",
publisher = "Oxford University Press",
number = "SUPPL. 2",

}

TY - JOUR

T1 - Steroidal regulation of biologically active luteinizing hormone secretion in men and women

AU - Veldhuis, Johannes D

AU - Dufa, M. L.

PY - 1993

Y1 - 1993

N2 - The biological activity of circulating luteinizing hormone (LH) molecules can be assessed with high sensitivity, specificity, and precision by the in-vitro rat interstitial (Leydig)-cell testosterone (RICT) bioassay. Compared to immunoreactive estimates of the LH content of plasma, the living Leydig-cell bioassay integrates the functional in-vitro potency of all circulating LH isoforms, while simultaneously reflecting the effects of otherwise potentially confounding in-vivo antagonists of LH action on steroidogenesis. Here, we review the pathophysiological regulation by steroid hormones of bioactive LH secretion and clearance in men and women. Our investigations and those in the available literature indicate that: (i) exogenous (non-aromatizable) 5-α-dihydrotestosterone infusion suppresses LH bioactivity, whereas blockade of the endogenous androgen receptor with flutamide increases secretion of biopotent LH in men; (ii) endogenous androgen excess due to a masculinizing testosterone-secreting adrenal tumour in a post-menopausal woman reversibly suppressed plasma LH bioactivity markedly; (iii) exogenous oestradiol infusion will reduce whereas the antioestrogen, tamoxifen HCl, can increase bioactive LH secretion in young men; (iv) the effect of anti-oestrogen is blunted in healthy older men; (v) endogenous hyperoestrogenism due to an adrenal oestrogen-secreting tumour in a middle-aged man with gynaecomastia profoundly but reversibly inhibited bioactive LH secretion; (vi) in post-menopausal women, exogenous oestrogen administration, whether oral (diethylstilbestrol), percutaneous (oestradiol), or intravaginal (oestradiolimpregnated silastic ring), exerts a temporally biphasic effect on basal bioactive LH secretion, i.e. acute suppression (within 24 h), subacute escape (at 5-10 days), and longer-term inhibition (30 days); (vii) during the normal menstrual cycle, bioactive LH secretion is pulsatile and both frequency and amplitude regulated; and (viii) oestrogen exposure can enhance gonadotrophin releasing hormone (GnRH)'s stimulatory action on biologically active LH secretion, resulting in so-called GnRH self-priming. Oestrogen's facilitative effects are achieved by a novel mechanism, in which oestrogen augments LH secretory burst mass and duration. Moreover, GnRH dose-LH secretory response studies show that oestrogen promotes an increase in GnRH efficacy (maximal effects) but not GnRH sensitivity (potency or half-maximally effective doses of GnRH). We conclude that steroid hormones are primary regulators of physiologically pulsatile bioactive LH secretion in healthy men and women. Moreover, steroids exert potent pathological effects on biologically active LH release in conditions of selective hyperandrogenism or hyperoestrogenism due to steroid-secreting adrenal or gonadal tumours.

AB - The biological activity of circulating luteinizing hormone (LH) molecules can be assessed with high sensitivity, specificity, and precision by the in-vitro rat interstitial (Leydig)-cell testosterone (RICT) bioassay. Compared to immunoreactive estimates of the LH content of plasma, the living Leydig-cell bioassay integrates the functional in-vitro potency of all circulating LH isoforms, while simultaneously reflecting the effects of otherwise potentially confounding in-vivo antagonists of LH action on steroidogenesis. Here, we review the pathophysiological regulation by steroid hormones of bioactive LH secretion and clearance in men and women. Our investigations and those in the available literature indicate that: (i) exogenous (non-aromatizable) 5-α-dihydrotestosterone infusion suppresses LH bioactivity, whereas blockade of the endogenous androgen receptor with flutamide increases secretion of biopotent LH in men; (ii) endogenous androgen excess due to a masculinizing testosterone-secreting adrenal tumour in a post-menopausal woman reversibly suppressed plasma LH bioactivity markedly; (iii) exogenous oestradiol infusion will reduce whereas the antioestrogen, tamoxifen HCl, can increase bioactive LH secretion in young men; (iv) the effect of anti-oestrogen is blunted in healthy older men; (v) endogenous hyperoestrogenism due to an adrenal oestrogen-secreting tumour in a middle-aged man with gynaecomastia profoundly but reversibly inhibited bioactive LH secretion; (vi) in post-menopausal women, exogenous oestrogen administration, whether oral (diethylstilbestrol), percutaneous (oestradiol), or intravaginal (oestradiolimpregnated silastic ring), exerts a temporally biphasic effect on basal bioactive LH secretion, i.e. acute suppression (within 24 h), subacute escape (at 5-10 days), and longer-term inhibition (30 days); (vii) during the normal menstrual cycle, bioactive LH secretion is pulsatile and both frequency and amplitude regulated; and (viii) oestrogen exposure can enhance gonadotrophin releasing hormone (GnRH)'s stimulatory action on biologically active LH secretion, resulting in so-called GnRH self-priming. Oestrogen's facilitative effects are achieved by a novel mechanism, in which oestrogen augments LH secretory burst mass and duration. Moreover, GnRH dose-LH secretory response studies show that oestrogen promotes an increase in GnRH efficacy (maximal effects) but not GnRH sensitivity (potency or half-maximally effective doses of GnRH). We conclude that steroid hormones are primary regulators of physiologically pulsatile bioactive LH secretion in healthy men and women. Moreover, steroids exert potent pathological effects on biologically active LH release in conditions of selective hyperandrogenism or hyperoestrogenism due to steroid-secreting adrenal or gonadal tumours.

KW - Bioactive

KW - Gonadotrophin

KW - Human

KW - Pituitary

KW - Pulsatile

UR - http://www.scopus.com/inward/record.url?scp=0027491348&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027491348&partnerID=8YFLogxK

M3 - Article

VL - 8

SP - 84

EP - 96

JO - Human Reproduction

JF - Human Reproduction

SN - 0268-1161

IS - SUPPL. 2

ER -