Nonclassical secretory dynamics of LH revealed by hypothalamo-hypophyseal portal sampling of sheep

A. Rees Midgley, Kristin McFadden, Mahmoud Ghazzi, Fred J. Karsch, Morton B. Brown, David T. Mauger, Vasantha Padmanabhan

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Continuous withdrawal of hypophyseal portal blood from unrestrained sheep has permitted detailed assessments of the pulsatile secretion of gonadotrophin-releasing hormone (GnRH). To determine if this blood can also be used to characterize the secretory dynamics of pituitary hormones, patterns of luteinizing hormone (LH) in the hypophyseal portal blood of ovariectomized ewes was compared with previous patterns of GnRH and peripheral LH. Hypophyseal portal blood and jugular vein blood were collected every 5 min from six ovariectomized ewes over 6-12 h. Hypophyseal portal blood contained GnRH-associated, sharply defined LH pulses that were much larger than in the periphery. Pulses of secreted LH (hypophyseal portal LH less peripheral LH) showed much faster rates of rise and fall than peripheral and followed pulses of GnRH by an average of 1.26 min. In contrast to pulses in jugular blood, secreted LH pulses often reached a relatively unchanging interpulse nadir-plateau and thereby approached closely algorithm-estimated, extrapolated baselines. The interpulse baseline concentrations of secreted LH (99.6 ng/mL) in hypophyseal portal blood were 31-fold higher than those for jugular LH (3.23 ng/mL). These elevated concentrations also exceeded mean jugular peak concentrations (11.1 ng/mL) and, thus, primarily must represent newly secreted LH. The non-Gaussian profiles of this secreted LH were substantially more complex than the inputs predicted from jugular LH measurements by deconvolution. Furthermore, regardless of the analytical approach, estimations of the mass of secreted LH in each pulse did not correlate well with inputs predicted by deconvolution or Kushler-Brown pulsefit analysis of corresponding pulses in jugular blood (r 2 ranging 0.40-0.48). Among alternative explanations is the possibility of heterogeneity in concentrations of GnRH in the portal vessels and variable distribution within the hypophysis. In summary, assay of hypophyseal portal blood obtained directly from the pituitary provides a method for direct assessment of secretory responses to hypothalamic peptides, and thereby serves as an unmatched method for studying the dynamics of LH secretion in vivo. With this approach, LH is revealed to be secreted as complex, non-Gaussian pulses that are far more sharply defined than those in the periphery, include non-GnRH-dependent, secretory components that cannot be predicted by deconvolution and are followed by periods of relatively constant, basal secretion.

Original languageEnglish (US)
Pages (from-to)133-143
Number of pages11
JournalEndocrine
Volume6
Issue number2
StatePublished - Jun 17 1997

Fingerprint

Luteinizing Hormone
Sheep
Gonadotropin-Releasing Hormone
Neck
Secretory Component
Pituitary Hormones
Jugular Veins
Pituitary Gland
Portal Vein

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Midgley, A. R., McFadden, K., Ghazzi, M., Karsch, F. J., Brown, M. B., Mauger, D. T., & Padmanabhan, V. (1997). Nonclassical secretory dynamics of LH revealed by hypothalamo-hypophyseal portal sampling of sheep. Endocrine, 6(2), 133-143.
Midgley, A. Rees ; McFadden, Kristin ; Ghazzi, Mahmoud ; Karsch, Fred J. ; Brown, Morton B. ; Mauger, David T. ; Padmanabhan, Vasantha. / Nonclassical secretory dynamics of LH revealed by hypothalamo-hypophyseal portal sampling of sheep. In: Endocrine. 1997 ; Vol. 6, No. 2. pp. 133-143.
@article{4a34bcaa53704ec09324853fa38cc110,
title = "Nonclassical secretory dynamics of LH revealed by hypothalamo-hypophyseal portal sampling of sheep",
abstract = "Continuous withdrawal of hypophyseal portal blood from unrestrained sheep has permitted detailed assessments of the pulsatile secretion of gonadotrophin-releasing hormone (GnRH). To determine if this blood can also be used to characterize the secretory dynamics of pituitary hormones, patterns of luteinizing hormone (LH) in the hypophyseal portal blood of ovariectomized ewes was compared with previous patterns of GnRH and peripheral LH. Hypophyseal portal blood and jugular vein blood were collected every 5 min from six ovariectomized ewes over 6-12 h. Hypophyseal portal blood contained GnRH-associated, sharply defined LH pulses that were much larger than in the periphery. Pulses of secreted LH (hypophyseal portal LH less peripheral LH) showed much faster rates of rise and fall than peripheral and followed pulses of GnRH by an average of 1.26 min. In contrast to pulses in jugular blood, secreted LH pulses often reached a relatively unchanging interpulse nadir-plateau and thereby approached closely algorithm-estimated, extrapolated baselines. The interpulse baseline concentrations of secreted LH (99.6 ng/mL) in hypophyseal portal blood were 31-fold higher than those for jugular LH (3.23 ng/mL). These elevated concentrations also exceeded mean jugular peak concentrations (11.1 ng/mL) and, thus, primarily must represent newly secreted LH. The non-Gaussian profiles of this secreted LH were substantially more complex than the inputs predicted from jugular LH measurements by deconvolution. Furthermore, regardless of the analytical approach, estimations of the mass of secreted LH in each pulse did not correlate well with inputs predicted by deconvolution or Kushler-Brown pulsefit analysis of corresponding pulses in jugular blood (r 2 ranging 0.40-0.48). Among alternative explanations is the possibility of heterogeneity in concentrations of GnRH in the portal vessels and variable distribution within the hypophysis. In summary, assay of hypophyseal portal blood obtained directly from the pituitary provides a method for direct assessment of secretory responses to hypothalamic peptides, and thereby serves as an unmatched method for studying the dynamics of LH secretion in vivo. With this approach, LH is revealed to be secreted as complex, non-Gaussian pulses that are far more sharply defined than those in the periphery, include non-GnRH-dependent, secretory components that cannot be predicted by deconvolution and are followed by periods of relatively constant, basal secretion.",
author = "Midgley, {A. Rees} and Kristin McFadden and Mahmoud Ghazzi and Karsch, {Fred J.} and Brown, {Morton B.} and Mauger, {David T.} and Vasantha Padmanabhan",
year = "1997",
month = "6",
day = "17",
language = "English (US)",
volume = "6",
pages = "133--143",
journal = "Endocrine",
issn = "0969-711X",
publisher = "Humana Press",
number = "2",

}

Midgley, AR, McFadden, K, Ghazzi, M, Karsch, FJ, Brown, MB, Mauger, DT & Padmanabhan, V 1997, 'Nonclassical secretory dynamics of LH revealed by hypothalamo-hypophyseal portal sampling of sheep', Endocrine, vol. 6, no. 2, pp. 133-143.

Nonclassical secretory dynamics of LH revealed by hypothalamo-hypophyseal portal sampling of sheep. / Midgley, A. Rees; McFadden, Kristin; Ghazzi, Mahmoud; Karsch, Fred J.; Brown, Morton B.; Mauger, David T.; Padmanabhan, Vasantha.

In: Endocrine, Vol. 6, No. 2, 17.06.1997, p. 133-143.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nonclassical secretory dynamics of LH revealed by hypothalamo-hypophyseal portal sampling of sheep

AU - Midgley, A. Rees

AU - McFadden, Kristin

AU - Ghazzi, Mahmoud

AU - Karsch, Fred J.

AU - Brown, Morton B.

AU - Mauger, David T.

AU - Padmanabhan, Vasantha

PY - 1997/6/17

Y1 - 1997/6/17

N2 - Continuous withdrawal of hypophyseal portal blood from unrestrained sheep has permitted detailed assessments of the pulsatile secretion of gonadotrophin-releasing hormone (GnRH). To determine if this blood can also be used to characterize the secretory dynamics of pituitary hormones, patterns of luteinizing hormone (LH) in the hypophyseal portal blood of ovariectomized ewes was compared with previous patterns of GnRH and peripheral LH. Hypophyseal portal blood and jugular vein blood were collected every 5 min from six ovariectomized ewes over 6-12 h. Hypophyseal portal blood contained GnRH-associated, sharply defined LH pulses that were much larger than in the periphery. Pulses of secreted LH (hypophyseal portal LH less peripheral LH) showed much faster rates of rise and fall than peripheral and followed pulses of GnRH by an average of 1.26 min. In contrast to pulses in jugular blood, secreted LH pulses often reached a relatively unchanging interpulse nadir-plateau and thereby approached closely algorithm-estimated, extrapolated baselines. The interpulse baseline concentrations of secreted LH (99.6 ng/mL) in hypophyseal portal blood were 31-fold higher than those for jugular LH (3.23 ng/mL). These elevated concentrations also exceeded mean jugular peak concentrations (11.1 ng/mL) and, thus, primarily must represent newly secreted LH. The non-Gaussian profiles of this secreted LH were substantially more complex than the inputs predicted from jugular LH measurements by deconvolution. Furthermore, regardless of the analytical approach, estimations of the mass of secreted LH in each pulse did not correlate well with inputs predicted by deconvolution or Kushler-Brown pulsefit analysis of corresponding pulses in jugular blood (r 2 ranging 0.40-0.48). Among alternative explanations is the possibility of heterogeneity in concentrations of GnRH in the portal vessels and variable distribution within the hypophysis. In summary, assay of hypophyseal portal blood obtained directly from the pituitary provides a method for direct assessment of secretory responses to hypothalamic peptides, and thereby serves as an unmatched method for studying the dynamics of LH secretion in vivo. With this approach, LH is revealed to be secreted as complex, non-Gaussian pulses that are far more sharply defined than those in the periphery, include non-GnRH-dependent, secretory components that cannot be predicted by deconvolution and are followed by periods of relatively constant, basal secretion.

AB - Continuous withdrawal of hypophyseal portal blood from unrestrained sheep has permitted detailed assessments of the pulsatile secretion of gonadotrophin-releasing hormone (GnRH). To determine if this blood can also be used to characterize the secretory dynamics of pituitary hormones, patterns of luteinizing hormone (LH) in the hypophyseal portal blood of ovariectomized ewes was compared with previous patterns of GnRH and peripheral LH. Hypophyseal portal blood and jugular vein blood were collected every 5 min from six ovariectomized ewes over 6-12 h. Hypophyseal portal blood contained GnRH-associated, sharply defined LH pulses that were much larger than in the periphery. Pulses of secreted LH (hypophyseal portal LH less peripheral LH) showed much faster rates of rise and fall than peripheral and followed pulses of GnRH by an average of 1.26 min. In contrast to pulses in jugular blood, secreted LH pulses often reached a relatively unchanging interpulse nadir-plateau and thereby approached closely algorithm-estimated, extrapolated baselines. The interpulse baseline concentrations of secreted LH (99.6 ng/mL) in hypophyseal portal blood were 31-fold higher than those for jugular LH (3.23 ng/mL). These elevated concentrations also exceeded mean jugular peak concentrations (11.1 ng/mL) and, thus, primarily must represent newly secreted LH. The non-Gaussian profiles of this secreted LH were substantially more complex than the inputs predicted from jugular LH measurements by deconvolution. Furthermore, regardless of the analytical approach, estimations of the mass of secreted LH in each pulse did not correlate well with inputs predicted by deconvolution or Kushler-Brown pulsefit analysis of corresponding pulses in jugular blood (r 2 ranging 0.40-0.48). Among alternative explanations is the possibility of heterogeneity in concentrations of GnRH in the portal vessels and variable distribution within the hypophysis. In summary, assay of hypophyseal portal blood obtained directly from the pituitary provides a method for direct assessment of secretory responses to hypothalamic peptides, and thereby serves as an unmatched method for studying the dynamics of LH secretion in vivo. With this approach, LH is revealed to be secreted as complex, non-Gaussian pulses that are far more sharply defined than those in the periphery, include non-GnRH-dependent, secretory components that cannot be predicted by deconvolution and are followed by periods of relatively constant, basal secretion.

UR - http://www.scopus.com/inward/record.url?scp=8244233839&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8244233839&partnerID=8YFLogxK

M3 - Article

C2 - 9225127

AN - SCOPUS:8244233839

VL - 6

SP - 133

EP - 143

JO - Endocrine

JF - Endocrine

SN - 0969-711X

IS - 2

ER -

Midgley AR, McFadden K, Ghazzi M, Karsch FJ, Brown MB, Mauger DT et al. Nonclassical secretory dynamics of LH revealed by hypothalamo-hypophyseal portal sampling of sheep. Endocrine. 1997 Jun 17;6(2):133-143.