Serum concentrations of dimeric inhibin during the spontaneous human menstrual cycle and after treatment with exogenous gonadotrophin

S MUTTUKRISHNA, Paul Alfred Francois Fowler, N P GROOME, G G Mitchell, W R Robertson, P G Knight

Research output: Contribution to journalArticle

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Abstract

A recently described two-site enzyme immunoassay incorporating a pre-assay oxidation step was validated and used to measure serum concentrations of dimeric inhibin in five normally cycling women and in 13 women undergoing gonadotrophin therapy. Recombinant human inhibin A (standard) gave an assay response curve which was parallel to those for human serum samples and recovery of exogenous inhibin added to serum samples before assay was quantitative (109 +/- 8%, n = 11). During the normal menstrual cycle dimeric inhibin concentration increased from 9.0 +/- 2.0 pg/ml during the early follicular phase to reach a mid-cycle peak of 55.3 +/- 11.1 pg/ml coincident with the pre-ovulatory gonadotrophin surge. After falling to 27.9 +/- 5.7 pg/ml 1 day after the luteinizing hormone surge, inhibin then rose in parallel with serum progesterone to reach a peak value of 115.6 +/- 19.3 pg/ml during the mid-luteal phase, before falling to 14.1 +/- 4.9 pg/ml by the onset of next menses. During the follicular phase, dimeric inhibin concentrations were closely correlated with those of serum oestradiol (r = 0.69; P < 0.001), whereas during the luteal phase they were most closely correlated with serum progesterone concentrations (r = 0.73; P < 0.001). Daily treatment with human menopausal gonadotrophin promoted a progressive increase in serum dimeric inhibin concentration which increased similar to 20-fold in 6 days. In the same period total ac-inhibin (measured by radioimmunoassay) increased -5-fold, while serum oestradiol increased similar to 30-fold. Although the assay cross-reacted with dimeric inhibin forms of molecular masses in the range 200-30 kDa, chromatography of superovulatory human serum revealed that the fully processed similar to 30 kDa form is the predominant circulating form, although a proportion of this (similar to 30%) is reversibly associated with serum binding protein(s).

Original languageEnglish
Pages (from-to)1634-1642
Number of pages9
JournalHuman Reproduction
Volume9
Issue number9
Publication statusPublished - Sep 1994

Keywords

  • dimeric inhibin
  • human serum
  • menstrual cycle
  • ovarian stimulation
  • 2-site immunoassay
  • follicle-stimulating-hormone
  • linked-immunoabsorbent-assay
  • common marmoset monkey
  • immunoreactive inhibin
  • Alpha-subunit
  • monoclonal-antibodies
  • ovarian inhibin
  • messenger-RNAS
  • corpus-luteum
  • bovine ovary

Cite this

MUTTUKRISHNA, S., Fowler, P. A. F., GROOME, N. P., Mitchell, G. G., Robertson, W. R., & Knight, P. G. (1994). Serum concentrations of dimeric inhibin during the spontaneous human menstrual cycle and after treatment with exogenous gonadotrophin. Human Reproduction, 9(9), 1634-1642.

Serum concentrations of dimeric inhibin during the spontaneous human menstrual cycle and after treatment with exogenous gonadotrophin. / MUTTUKRISHNA, S ; Fowler, Paul Alfred Francois; GROOME, N P ; Mitchell, G G ; Robertson, W R; Knight, P G.

In: Human Reproduction, Vol. 9, No. 9, 09.1994, p. 1634-1642.

Research output: Contribution to journalArticle

MUTTUKRISHNA, S, Fowler, PAF, GROOME, NP, Mitchell, GG, Robertson, WR & Knight, PG 1994, 'Serum concentrations of dimeric inhibin during the spontaneous human menstrual cycle and after treatment with exogenous gonadotrophin', Human Reproduction, vol. 9, no. 9, pp. 1634-1642.
MUTTUKRISHNA, S ; Fowler, Paul Alfred Francois ; GROOME, N P ; Mitchell, G G ; Robertson, W R ; Knight, P G. / Serum concentrations of dimeric inhibin during the spontaneous human menstrual cycle and after treatment with exogenous gonadotrophin. In: Human Reproduction. 1994 ; Vol. 9, No. 9. pp. 1634-1642.
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AU - Robertson, W R

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N2 - A recently described two-site enzyme immunoassay incorporating a pre-assay oxidation step was validated and used to measure serum concentrations of dimeric inhibin in five normally cycling women and in 13 women undergoing gonadotrophin therapy. Recombinant human inhibin A (standard) gave an assay response curve which was parallel to those for human serum samples and recovery of exogenous inhibin added to serum samples before assay was quantitative (109 +/- 8%, n = 11). During the normal menstrual cycle dimeric inhibin concentration increased from 9.0 +/- 2.0 pg/ml during the early follicular phase to reach a mid-cycle peak of 55.3 +/- 11.1 pg/ml coincident with the pre-ovulatory gonadotrophin surge. After falling to 27.9 +/- 5.7 pg/ml 1 day after the luteinizing hormone surge, inhibin then rose in parallel with serum progesterone to reach a peak value of 115.6 +/- 19.3 pg/ml during the mid-luteal phase, before falling to 14.1 +/- 4.9 pg/ml by the onset of next menses. During the follicular phase, dimeric inhibin concentrations were closely correlated with those of serum oestradiol (r = 0.69; P < 0.001), whereas during the luteal phase they were most closely correlated with serum progesterone concentrations (r = 0.73; P < 0.001). Daily treatment with human menopausal gonadotrophin promoted a progressive increase in serum dimeric inhibin concentration which increased similar to 20-fold in 6 days. In the same period total ac-inhibin (measured by radioimmunoassay) increased -5-fold, while serum oestradiol increased similar to 30-fold. Although the assay cross-reacted with dimeric inhibin forms of molecular masses in the range 200-30 kDa, chromatography of superovulatory human serum revealed that the fully processed similar to 30 kDa form is the predominant circulating form, although a proportion of this (similar to 30%) is reversibly associated with serum binding protein(s).

AB - A recently described two-site enzyme immunoassay incorporating a pre-assay oxidation step was validated and used to measure serum concentrations of dimeric inhibin in five normally cycling women and in 13 women undergoing gonadotrophin therapy. Recombinant human inhibin A (standard) gave an assay response curve which was parallel to those for human serum samples and recovery of exogenous inhibin added to serum samples before assay was quantitative (109 +/- 8%, n = 11). During the normal menstrual cycle dimeric inhibin concentration increased from 9.0 +/- 2.0 pg/ml during the early follicular phase to reach a mid-cycle peak of 55.3 +/- 11.1 pg/ml coincident with the pre-ovulatory gonadotrophin surge. After falling to 27.9 +/- 5.7 pg/ml 1 day after the luteinizing hormone surge, inhibin then rose in parallel with serum progesterone to reach a peak value of 115.6 +/- 19.3 pg/ml during the mid-luteal phase, before falling to 14.1 +/- 4.9 pg/ml by the onset of next menses. During the follicular phase, dimeric inhibin concentrations were closely correlated with those of serum oestradiol (r = 0.69; P < 0.001), whereas during the luteal phase they were most closely correlated with serum progesterone concentrations (r = 0.73; P < 0.001). Daily treatment with human menopausal gonadotrophin promoted a progressive increase in serum dimeric inhibin concentration which increased similar to 20-fold in 6 days. In the same period total ac-inhibin (measured by radioimmunoassay) increased -5-fold, while serum oestradiol increased similar to 30-fold. Although the assay cross-reacted with dimeric inhibin forms of molecular masses in the range 200-30 kDa, chromatography of superovulatory human serum revealed that the fully processed similar to 30 kDa form is the predominant circulating form, although a proportion of this (similar to 30%) is reversibly associated with serum binding protein(s).

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KW - messenger-RNAS

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