We found that human saliva contains both insulin-like growth factor I (IGF-I) and IGF-II but no significant binding proteins, and that salivary IGF-I levels correlated with plasma GH levels. Mixed saliva had globular proteins precipitated by freezing/thawing. After centrifugation the clear supernatant was used directly in the IGF-I RIA (Van Wyk and Underwood antibody) and in a human placental membrane RRA for IGF-II. The lower limits of detection for IGF-I and IGF-II were 0.7 ng/mL (micrograms/L) and 1.2 ng/mL (micrograms/L), respectively. Iodinated IGF added to saliva was not degraded, as assessed by trichloroacetic acid precipitability and placental membrane binding. In saliva from 14 normal subjects, IGF-I was measurable in all. IGF-II was detectable only in 8 of 14 subjects; the mean value in these 8 subjects was 2.6 +/- 0.6 (+/- SE) ng/mL (micrograms/L). The mol wt of salivary IGF was similar to that of free plasma IGF after acid or neutral pH gel chromatography. Human saliva contained no significant IGF-binding protein. Eluates from neutral gel chromatography of concentrated (20-fold) normal saliva did not inhibit IGF-II binding to placental membrane receptors. Eluted proteins from saliva samples subjected to prior acid gel chromatography failed to bind radiolabeled IGF after neutralization. Saliva samples assayed for binding protein using an amniotic fluid binding protein RIA had values at or below the lower limit of detection [less than 0.06 micrograms eq/mL (mgeq/L)]. Salivary IGF-I concentrations did not change with increasing salivary flow rates above normal, with time of day, or with storage at room temperature for up to 24 h before freezing. The mean IGF-I concentration in mixed saliva from 14 normal young adults (8 men) was 2.3 +/- 0.3 (+/- SE) ng/mL (micrograms/L), and their mean plasma IGF-I level was 315 +/- 27 ng/mL (micrograms/L). Mean salivary IGF-I was significantly lower in 15 patients with GH deficiency [1.3 +/- 0.2 ng/mL (micrograms/L); P less than 0.01] and 8-fold higher in 5 acromegalic patients [17.2 +/- 6.3 ng/mL (micrograms/L); P less 0.01]. Removal of their GH adenomas led to a fall in salivary IGF-I to 5.6 +/- 1.3 ng/mL (micrograms/L); P less than 0.05). In summary, saliva contains free IGFs but no significant quantities of specific binding proteins. Salivary IGF-I levels reflect the GH status of the donor.
Insulin-like growth factor-I (IGF-I) is a GH-dependent growth factor found in its highest concentrations in plasma. It is also measurable in saliva. The origins of salivary IGF-I concentrations were studied. Intracardial administration of Sprague-Dawley rats with 125I-labelled IGF-I and subsequent analysis of plasma and saliva samples by exclusion gel chromatography and SDS-PAGE, followed by autoradiography, demonstrated the apparent inability of IGF-I to cross from the plasma pool through to saliva. 125I-Labelled IGF-I was not chromatographed immediately before injection, resulting in administration of free iodide along with the iodinated peptide. This free iodide was demonstrable in saliva, indicating that movement of substances from plasma to saliva was measurable using the levels of 125I activity administered. Free iodide in saliva was not contributed to by 125I-labelled IGF-I degradation since 125I-labelled IGF-I was shown to be stable in saliva over 24 h. These data indicated that IGF-I in saliva is produced locally. Identification of a 4.7 kb IGF-I mRNA transcript in rat parotid salivary gland was consistent with IGF-I synthesis within that tissue.
The chronic administration of the long-acting LHRH agonist analog D-Ser(TBU)6-LHRH-EA10 (HOE 766, Buserelin) suppresses pituitary gonadotropin secretion. Since a similar analog was shown to be effective in the short term parenteral treatment of idiopathic precocious puberty in girls (10), we used Buserelin both intranasally and sc to treat patients of both sexes with idiopathic and secondary central precocious puberty to test its efficacy, safety, and potential for long term use. Six girls and two boys presented with advanced skeletal maturity, accelerated growth velocity, Tanner stage II-IV pubertal development, and pubertal levels of sex steroids and gonadotropins. Patients were treated for 6 months sc and up to 5 months intranasally. Optimal doses ranged from 10-20 micrograms/kg X day in girls and 30 micrograms/kg X day in boys, with marked individual variation. During sc therapy, there was significant suppression of growth velocity (P less than 0.001), serum gonadotropins (P less than 0.001), 17 beta-estradiol (P less than 0.005), and testosterone as well as clinical and behavioral improvement. The rate of bone maturation was reduced. All effects were reversed after discontinuation of therapy for 1 month in one girl. No reduction in efficacy was seen after changing four girls and one boy to intranasal therapy, but improved acceptability and compliance were reported by parents. Apart from withdrawal bleeding in one girl and transient acceleration of puberty in two patients during the initial phase of treatment, no serious unwanted effects occurred. Antibodies to native LHRH were not detected after 6 months of therapy. These results confirm the efficacy and safety of Buserelin by intranasal and sc routes in patients with sexual precocity and indicate a need for long term studies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.