title: Growth hormone (GH)-binding protein regulation by estrogen, progesterone, and gonadotropins in human: the effect of ovulation induction with menopausal gonadotropins, GH, and gestation.
abstract: The recently described serum GH-binding protein (GH-BP) may reflect the GH-receptor level. To assess the serum GH-BP levels under various physiological and supraphysiological levels of sex steroids, we have evaluated its concentration in 26 patients undergoing 34 cycles of ovulation induction with either human menopausal gonadotropins (hMG)/hCG or GH/hMG/hCG. The latter ovulation induction protocol was undertaken in "Clonidine negative" patients in a prospective, randomized, crossed-over manner, between GH/hMG/hCG or hMG/hCG. The increase in GH-BP levels in patients' sera undergoing ovulation induction directly correlated with peripheral estradiol (E2) (r = 0.577; P < 0.001), and with peripheral progesterone (P4) (r = 0.542; P < 0.001; n = 174) concentrations in hMG/hCG cycles, and also in GH/hMG/hCG cycles (r = 0.669, P < 0.001 for E2, and r = 0.722, P < 0.001 for P4, n = 84). GH-BP levels did not change significantly in response to 0.15 mg Clonidine ingestion. The baseline GH-BP levels significantly correlated with the body mass index of 47 patients (r = 0.547; P < 0.001). The insulin-like growth factor-I (IGF-I) concentrations increased in correlation with increasing E2 levels up to 5500 pmol/L but decreased thereafter, at very high E2 concentrations. In gestations generated by ovulation induction with hMG/hCG or GH/hMG/hCG, longitudinal measurements of GH-BP levels showed an initial sharp increase during early gestation, followed by a gradual decrease beginning around the end of the first trimester and continuing during the mid and late trimesters. In normal spontaneous pregnancies, GH-BP levels, measured from the fifth week until term, were negatively correlated with gestational age (r = -0.581; P < 0.001; n = 84). This pattern is highly suggestive of the possibility that GH-BP is coregulated not only with E2 and P4 but also with hCG, and possibly other gonadotropins as well. Indeed, in patients with "resistant ovaries", pharmacological amounts of hMG failed to increase E2 concentrations but moderately increased GH-BP levels. These data provide good indirect evidence for coregulation of the GH-BP with both sex steroids and gonadotropins. The mid and late trimesters decrease in GH-BP levels in spite of increasing sex steroids concentrations, may be attributed to the decreasing hCG concentrations, and/or to the increasing secretion of placental lactogen (PL) and placental GH with the advancing gestation.
authors.affiliation: Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Z
authors.initials: Z
authors.lastname: Blumenfeld
authors.forename: R J
authors.initials: RJ
authors.lastname: Barkey
authors.forename: M B
authors.initials: MB
authors.lastname: Youdim
authors.forename: J M
authors.initials: JM
authors.lastname: Brandes
authors.forename: T
authors.initials: T
authors.lastname: Amit
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D005260:Female; D006062:Gonadotropins / Q000502:physiology*; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008596:Menotropins / Q000494:pharmacology; D010062:Ovulation Induction; D011247:Pregnancy / Q000378:metabolism*; D011374:Progesterone / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D006063:Chorionic Gonadotropin; D004967:Estrogens; D006062:Gonadotropins; D011374:Progesterone; D008596:Menotropins; D013006:Growth Hormone; C051815:somatotropin-binding protein