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Biomedical subjects

K C Copeland

Publications and source records attributed to K C Copeland.

68 records · Page 4Linked to original sources

Estrogen stimulates growth hormone and somatomedin-C in castrate and intact female baboons.

To evaluate the effects of physiological concentrations of estrogen on plasma concentrations of somatomedin-C (Sm-C) and GH, 16 chronic castrate female baboons were implanted either with blank Silastic capsules (n = 5) or capsules containing crystalline estradiol (E2; n = 11), which remained in place for 7 days. By day 7, serum E2 levels in treated animals rose into the physiological adult female range (mean +/- SEM, 96 +/- 9.2 pg/ml) and were greater (P less than 0.0005) than those in control animals (27.5 +/- 3.4 pg/ml). Sm-C concentrations rose significantly by day 7 in treated animals compared to those in control animals, whether assayed from unprocessed plasma (96% increase; P less than 0.01), plasma pretreated with glycine-HCl (99% increase; P less than 0.01), or plasma extracted with acid-ethanol (72% increase; P less than 0.02). GH concentrations in these animals were low and were not significantly different in E2-treated and control animals. To evaluate the effects of pharmacological doses of E2 on Sm-C and GH concentrations, six intact adult female baboons were treated with six daily injections of 1 mg E2 benzoate in oil. Serum E2 rose to a mean level of 1669 +/- 320 pg/ml on day 7. The plasma Sm-C concentration by day 7 was significantly higher than the pretreatment value whether assayed in untreated plasma (4.3-fold increase; P less than 0.01), plasma pretreated with glycine-HCl (2-fold increase; P less than 0.01), or plasma extracted with acid-ethanol (1.7-fold increase; P less than 0.01). Mean serum GH concentrations rose significantly from 3.3 ng/ml on day 0 to 23.6 ng/ml by day 7 (P less than 0.02). Evaluation of the chromatographic profile of native baboon plasma suggested a marked increase in [125I]Sm-C binding to plasma proteins after in vivo pharmacological E2 treatment; a broad peak of [125I]Sm-C binding over a size range from that of albumin to gamma-globulin was found. These results indicate that estrogen treatment of castrate or intact female baboons with both physiological and pharmacological doses results in an increase in plasma Sm-C concentrations that, at least in pharmacological doses, are mediated through an increase in GH concentrations. Although pharmacological E2 treatment results in a stimulation of plasma proteins that bind Sm-C, the effects on plasma Sm-C concentrations were found after procedures that diminish interference from circulating binding proteins. These data support the concept that estrogen may play a role in the physiological increase in plasma concentrations of Sm-C associated with normal puberty.

Animals↗

Effect of in vitro action of serum proteases or exposure to acid on measurable immunoreactive somatomedin-C in serum.

The proportion of immunoreactive somatomedin-C (IR-Sm-C) in blood that is available for measurement in the RIA is influenced by whether the sample is processed as serum or plasma, by how promptly the sample is chilled and frozen, by whether the reaction is carried out in glass or polystyrene tubes and by whether the incubation mixture contains protamine or heparin. Although protamine buffers and polystyrene tubes increase the availability of purified somatomedin-C (Sm-C), they decrease the detectability of Sm-C in serum. By incubating serum at neutral or acid pH, this IR-Sm-C can be made available for measurement, suggesting that incubation alters the nature of the linkage between Sm-C and its binding proteins or causes a conformational change in the binding protein, resulting in greater exposure of IR-Sm-C. The increment in measurable IR-Sm-C that occurs at neutral pH appears to be due to the action of proteolytic enzymes since it is time, temperature, and pH dependent and is inhibited by a variety of protease inhibitors and chelating agents. The increment which occurs at acid pH is not inhibited by chelating agents or elevated temperature and must be due in part to acid hydrolysis of Sm-C and its binding proteins. However, since the acid-induced increment is optimal within a narrow pH range and falls off sharply below pH 3.5, acid proteases may also be involved. These observations, which provide insight into the nature of the serum proteins with which Sm-C is associated, bear on the interpretation of results of serum somatomedin measurements carried out with different methods. They also may aid in delineating the mechanisms by which the somatomedin contained in the macromolecular complex in serum is made available to tissues.

Adolescent↗

Pubertal endocrinology of the baboon: elevated somatomedin-C/insulin-like growth factor I at puberty.

Previous data suggested an increase in the rate of weight gain and linear growth in the baboon between 3 and 4 yr of age, similar to the pubertal growth spurt in man. In this cross-sectional study, radioimmunoassayable concentrations of somatomedin-C/insulin-like growth factor I(SM-C/IGF-I) were compared in prepubertal (less than 3 yr), pubertal (3-4 yr), and adult (greater than 10 yr) animals. SM-C/IGF-I concentrations in prepubertal males (0.97 +/- 0.10 U/ml) were low and were not different from those in prepubertal females (0.98 +/- 0.15 U/ml). Between 3 and 4 yr, SM-C/IGF-I increased significantly in both sexes (8.87 +/- 0.74 and 5.27 +/- 0.52 U/ml, male and female, respectively) and decreased (5.92 +/- 1.2 and 2.75 +/- 0.13 U/ml, respectively) in animals greater than 10 yr of age. Sex differences were significant in the 3- to 4-yr-old animals (male greater than female, P less than 0.001). The pubertal elevation in SM-C/IGF-I concentrations is coincident with increases in indices of somatic growth and sexual maturation in the baboon. These and other data suggest that this animal may be an appropriate model for studies to define hormonal mechanisms of pubertal growth.

Animals↗

Development of a heterologous radioimmunoassay for somatomedin C in sheep blood.

A heterologous radioimmunoassay for the measurement of somatomedin C in sheep serum has been developed using purified 125I-labelled human somatomedin C and an antiserum to human somatomedin C. It was observed that the GH dependence of somatomedin C could not be verified when unprocessed sheep sera were assayed, because of interference by somatomedin binding proteins. After incubation of samples at pH 3.8, however, concentrations of somatomedin C mirrored GH status. Assays results from sera after prolonged exposure to acid agreed with results from which had undergone acidification and gel chromatography. Using the methods developed in this study, 12 sera from normal sheep had a mean concentration of somatomedin C of 2.35 +/- 0.27 (S.E.M.) units/ml while nine sera from hypophysectomized sheep contained 0.45 +/- 0.04 units/ml (P less than 0.001), and one serum from a ewe with a prolonged GH excess associated with a pituitary tumour had a value of 6.9 units/ml. The radioimmunoassay resulting from these studies should provide a tool for investigation of the physiological control of somatomedin C in sheep.

Animals↗

Pseudogynecomastia due to neurofibromatosis--a light microscopic and ultrastructural study.

A six year old boy with bilateral breast enlargement was found to have a normal endocrine status. Resected tissue revealed the features of pseudogynecomastia due to a proliferation of fibrous tissue traversed by neuroid structures. Multinucleated giant cells were present within the fibrous tissue. Ultrastructural study revealed organized nerve elements in a collagenous stroma. The multinucleated giant cells appeared to be variants of the predominant stromal fibroblasts.

Breast↗

[Urinary LHRH: radioimmunological assay and physiological significance].

A LHRH-like substance is detectable in the urine. It is extractable by glass powder, which suggests that it is a peptide, and it can be concentrated by anti-LHRH affinity chromatography, strongly suggesting that it is not a contaminant in the RIA. It is composed of very little intact LHRH, and the great majority appears as multiple smaller fractions, although the possibility of "urinary LHRH" being a slightly larger peptide containing a sequence similar or identical to that of LHRH has not been entirely eliminated. Urinary measurements show no correlation with the clinical state, and the widely differing values obtained using different antisera in the present study emphasize the need for in-depth antiserum binding studies prior to clinical use in the LHRH radioimmunoassay.

Adult↗

The secretion of adrenal androgens and growth patterns of patients with hypogonadotropic hypogonadism and isiopathic delayed puberty.

Plasma concentrations of adrenal androgens (DHEA and DHEA-S) and the growth patterns of four male patients with hypogonadotropic hypogonadism have been compared and contrasted with those of eight male patients wit idiopathic delayed puberty. As a group the patients with HH presented at an older age with delayed puberty and normal heights; the growth rate and pattern have been normal except for an absence of the pubertal growth spurt. Adrenal androgens were usually normal for chronologic age and high for bone age. The patients with IDP presented at a younger age, usually with short stature, low adrenal androgens relative to the chronologic age, but normal relative to the bone age. Patients with IDP appear to exhibit a delay in maturation of both the adrenal cortex and the hypothalamo-pituitary gonadal axis usually with short stature and retardation of the bone age. The importance in measurements of adrenal androgens in the diagnosis of HH and of IDP is emphasized.

Adolescent↗