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Biomedical subjects

A W Root

Publications and source records attributed to A W Root.

At least 91 records · Page 5Linked to original sources

Further studies of the effects of intravenous infusion or intramuscular injection of gonadotropin-releasing hormone during childhood and adolescence.

To provide data on the readily releasable pools of pituitary gonadotropins and to compare routes of administration, gonadotropin-releasing hormone (Gn-RH, 100 micrograms) was administered to 135 endocrinologically normal children and adolescents by continuous intravenous 3-hour infusion or by acute intramuscular injection. The Gn-RH infusion resulted in a significant four- and sevenfold increase in serum luteinizing hormone (LH) values in prepubertal subjects and pubertal males, respectively. A 14-fold increment, biphasic in appearance, occurred in pubertal females. Gn-RH-induced serum follicle-stimulating hormone (FSH) increases were greater in females than in males. Following intramuscular injection of Gn-RH, a monophasic increment of serum LH and FSH occurred. LH rises were greater in pubertal than in prepubertal children and greater in females than in males. FSH increments were greater in females than in males, prepubertal being slightly greater than pubertal. Urinary gonadotropin excretion mirrored the changes in the serum samples. These results in the largest reported group of normal children generally confirm those of previous reports except for the greater Gn-RH-evoked releasable LH in pubertal females than in males.

Adolescent↗

Urinary excretion of immunoreactive luteinizing hormone-releasing hormone-like material in children correlation with pubertal development.

Immunoreactive LRH (iLRH)-like material has been measured in extracts of urine from normal children and adolescents, adult men and women, and postmenopausal women. The urinary excretion of iLRH-like material was significantly greater in pubertal than in prepubertal subjects and in boys than girls at both stages of sexual maturation [prepubertal males, 3.26 +/- 0.49 ng/24 h (SE; n = 24); pubertal males, 5.94 +/- 1.36 (n = 12); prepubertal females, 1.14 +/- 0.21 (n = 19); pubertal females, 2.85 +/- 0.56 (n = 13)]. In adult males (n = 5) the urinary excretion of iLRH-like material was 7.8 +/- 1.3 ng/24 h, and in adult women in the follicular phase of the menstrual cycle (n = 8) it was 2.9 +/- 0.3. In five postmenopausal women the urinary iLRH-like content was 7.32 +/- 0.92 ng/24 h (P less than 0.01 relative to normal pubertal and adult women). In children the 24-h urinary excretion of iLRH-like material was positively correlated with chronological and bone ages, Tanner stage of genital (male) and breast (female) development, and the urinary excretion of LH and FSH in males. It did not correlate with the urinary excretion of either LH or FSH in females. Carboxymethylcellulose chromatography of extracts of urine from pubertal boys and girls, adult men and women, and postmenopausal women suggested that the iLRH-like material may be the 2-10 fragment of LRH rather than the intact decapeptide.

Adolescent↗

Responses to constant infusion of LH-RH in girls with primary hypogonadism.

To further assess quantitative pituitary gonadotropin release in patients with primary hypogonadism, a 3-hour constant infusion of the synthetic gonadotropin-releasing hormone, LH-RH, was administered to 12 functionally agonadal girls (11 with Turner syndrome and 1 who had been overiectomized), aged 9.5 to 19.42 years. Gonadotropin and sex steroid responses were determined before and during the infusion and contrasted to those in normal pubertal females. in girls with skeletal age under 11 years, mean control LH increased (P < .001) from 2.2 +/- 0.3 (mean +/- SEM) mIU/ml to 21.3 +/- 7.3 during LH-RH infusion, while luteinizing hormone (LH) rose (P < .001) from 89.2 +/- 24.6 to 276.5 +/- 42.6 girls with skeletal age over 11 years. This age-related augmentation is an exaggeration of data in normal girls and occcurs despite minimal gonadal secretion of sex steroids. A similar age-related discrepancy was not seen in follicle-stimulating hormone (FSH) secretion evoked by LH-RH; all girls had FSH increments into the castrate range with a rise from mean control levels of 78.6 +/- 6.7 to 133.9 +/- 8.3. These data demonstrate an age-related increase in LH-RH-evoked LH secretion, but not of FSH, in children and adolescents with primary hypogonadism.

Adolescent↗

Changes in 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D during pregnancy.

Serum concentrations of 25-hydroxyvitamin D (25OHD) and 24,25-dihydroxyvitamin D (24,25(OH)2D) were measured in a cross-sectional study of 94 normal pregnant women at various stages of gestation in order to assess the hormonal regulation of calcium homeostasis during gestation. The 40 week gestational period was divided into four 10 weeks quarters. 25OHD concentration were significantly below control levels (32.2 +/- 3.1 (S.E.) ng/ml) by the second quarter of pregnancy and were even lower at term. Serum levels of 24,25(OH)2D did not decrease until the fourth quarter, when the mean concentration (0.8 +/- 0.1 ng/ml) was approximately one half the control values (1.5 +/- 0.3, p less than 0.025). These data suggest that the metabolic pathways of vitamin D are altered during gestation, perhaps in response to increasing mother-to-fetus transport of calcium. There is decreased 24-hydroxylation and, in view of the lowered 25OHD levels, possibly increased production of 1,25-hydroxyvitamin D (1,25(OH)2D).

Chorionic Gonadotropin↗

Serum concentrations of 24,25(OH)2D in uremic children: a reflection of renal function.

The mean serum concentration of 24,25(OH)2D determined by competitive protein-binding radioassay was significantly lower in ten uremic children maintained on hemodialysis (0.82 +/- 0.43[SD] ng/ml) than in ten patients with impaired renal function not requiring hemodialysis (1.30 +/- 0.54 ng/ml, P less than 0.05), or in 12 normal children (2.98 +/- 1.57 ng/ml, P less than 0.01). The serum levels of 250HD were similar in all groups. There were significant (P less than 0.01) positive correlations between the serum concentration of 24,25(OH)2D or the ratio 24,25(OH)2D/25OHD and the creatinine clearance. The serum concentration of 24,25(OH)2D was significantly decreased also in six anephric adults relative to normal adult values. The data indicate that production of 24,25(OH)2D is impaired in subjects with compromised renal function. Inasmuch as the major active metabolite of Vitamin D, i.e., 1,25(OH)2D, is requried for renal synthesis of 24,25(OH)2D measurement of the latter metabolite may provide a convenient method for assessment of renal vitamin D metabolism. The role of this metabolite in the pathogenesis of renal osteodystrophy remains speculative.

Child↗

Effects of zinc deficiency upon pituitary function in sexually mature and immature male rats.

Serum pituitary levels of growth hormone (GH), thyrotropin (TSH), prolactin (PRL), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured in sexually mature (adult) and sexually immature (juvenile) male rats who had been deprived of dietary zinc for 15 and 7 weeks, respectively. When compared to pair-fed control rats receiving a zinc supplemented diet, both the adult and juvenile zinc deficient rats had significantly lower body weights, tail lengths and ventral prostate weights. The testes of the sexually immature rats were also smaller than those of the pair-fed animals. In sexually mature, zinc deficient rats serum concentrations of GH and testosterone were significantly lower and serum LH levels significantly higher than in ad libitum fed control rats. Pituitary and hypothalamic levels of other hormones did not differ from values recorded in control animals. In sexually immature zinc deficient rats serum concentrations of GH were also significantly depressed; pituitary content and concentration of LH and pituitary and serum levels of FSH were significantly increased over control values. No discernible effects of zinc deficiency upon hyplthalamic content of LH-releasing hormone or serum concentrations of PRL or TSH were recorded in juvenile rats. Zinc deficiency has minimal effects upon the hypothalamic-pituitary axis of sexually mature rats. In sexually immature males, zinc deprivation leads to impairment of gonadal growth and increased synthesis and/or secretion of the pituitary gonadotropins.

Aging↗

Synthesis of 1,25-dihydroxyvitamin D in the nephrectomized pregnant rat.

Pregnant rats were maintained on diets either adequate or deficient in vitamin D. On the 20th day of gestation, animals were either nephrectomized bilaterally or sham operated. Immediately therafter, four groups of nephrectomized or sham-operated pregnant rats received iv [26,27-3H]25-hydroxyvitamin D3 ([26,27-3H]25OHD3), while two groups received [1,2-3H,4-14C]D3. The animals were sacrificed 10-24 h later. The distribution of the radiolabeled metabolites of vitamin D3 was determined in extracts of maternal plasma, maternal intestinal tract, placentae, and fetuses after Sephadex LH-20 column chromatography. Both vitamin D3 and 25OHD3 crossed the placenta and entered the fetus. In anephric animals receiving [26,27-3H]-25OHD3, 24,25-dihydroxyvitamin D and a polar peak eluting in the position of 1,25-dihydroxyvitamin D [1,25(OH)2D] and 25,26-dihydroxyvitamin D were identified in extracts of maternal plasma and intestinal tracts and of placentae and fetuses. The identities of 24,25-dihydroxyvitamin D and 1,25 (OH)2D were confirmed by high pressure liquid chromatography. In rats receiving [1,2-3H,4-14C]D3, approximately 50% of the polar metabolite consisted of 1,25(OH)2D. We conclude that the anephric pregnant rat is able to synthesize 1,25(OH)2D, that the fetal portion of the feto-placental unit is the most likely site of production of this hormone, and that this metabolite of vitamin D is able to cross the placenta from the fetus to the mother.

Animals↗

Effect of pyridoxine on pituitary release of growth hormone and prolactin in childhood and adolescence.

The dopamine agonist, pyridoxine, was administered to 10 children being evaluated for short stature. Serum GH and PRL responses were contrasted to those after insulin-induced hypoglycemia (ITT) and L-dopa administration. Levels of GH did not change after pyridoxine, but PRL fell (P less than 0.05) to 42% of the zero time concentration. Significant increments of GH occurred during ITT and after L-dopa, while PRL was suppressed to a greater extent by L-dopa. We conclude that pyridoxine is not useful in assessment of hypothalamic-pituitary function.

Adolescent↗

Sequential use of insulin and levodopa to provoke pituitary secretion of growth hormone.

More than one method of stimulating human growth hormone (hGH) release is necessary to adequately evaluate the secretory capacity of pituitary somatotropes. In this study, sequential insulin-induced hypoglycemia (ITT) and oral administration of levodopa were used to study hGH release in 30 short normal children and adolescents and in five children with hypopituitarism. In the normal subjects, hGH levels greater than 5 ng/ml were achieved in 26 of 30 with the ITT and in 28 of 30 following administration of levodopa. Each of the normal children responded to at least one test. None of the children with hypopituitarism demonstrated hGH secretion during the study. We conclude that sequential administration of insulin and levodopa is a reliable, convenient, and safe method of assessing the release of hGH by the pituitary somatotropes during childhood.

Adolescent↗

Effect of an infusion of Gn-RH upon levels of sex hormones in prepubertal and pubertal girls: evidence for relative ovarian insensitivity.

Changes in levels of sex steroids and gonadotropins were measured in 16 normal prepubertal and 15 pubertal girls prior to and after a 3 hour infusion of 100 microgrm synthetic gonadotropin releasing hormone (Gn-RH). Plasa estradiol (E2) concentrations rose significantly (p less than 0.02) from 29.7 +/- 4.6 (SE) pg/ml in the basal period to to 46.8 +/- 7.1 at the end of the infusion in the pubertal girls but were unchanged in the prepubertal girls. Estrone (E1), progesterone (P), 17-HYDROXYPROGESTERONE (17OHP), TESTOSTERONE (T), DIHYDROTESTOSTERONE (DHT), and androstenedione (A), dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulfate (DHAS) levels were not altered in either maturity group. Basal plasma E2, E1, T, DHT, DHA and DHAS concentrations significantly correlated with the releasable pool of LH evoked by Gn-RH from the pituitary gonadotropes. We conclude: 1) The ovary is not highly and rapidly responsive to transient elevations of endogenous gonadotropin, and 2) Adrenal androgens may to some extent modulate the maturation of the hypothalamic-pituitary-gonadal system, at least as reflected by the pituitary response to exogenous Gn-RH.

Adolescent↗

Secretion of the adrenal androgen, dehydroepiandrosterone sulfate, during normal infancy, childhood, and adolescence, in sick infants, and in children with endocrinologic abnormalities.

Serum concentrations of the adrenal androgen, dehydroepiandrosterone sulfate, were measured by radioimmunoassay in normal infants and children, in sick premature and full-term newborn infants, and in patients undergoing evaluation of the hypothalamic-pituitary-gonadal and -adrenal systems. Premature infants had significantly greater (p less than 0.001) levels of DHAS (263 +/- 40)[SE]migrong/dl) than did full-term infants (58.9 +/- 5.2) during the first ten days of life; further increments occurred in stressed "sick" infants. A gradual age- and maturity-related rise in serum concentrations of DHAS was observed during childhood with the earliest increase occurring prior to the onset of pubertal production of gonadal steroids. Serum levels of DHAS rose following administration of ACTH and were increased in patients with congenital adrenal hyperplasia, in whom rapid decrements followed treatment with dexamethasone. hCG or LH-RH treatment did not alter DHAS concentrations. These data suggest that direct secretion of DHAS by the adrenal gland and/or peripheral sulfation of DHA, rather than gonadal secretion, accounts for the majority of DHAS production. The involvement of adrenal androgens in the pubertal maturation of the reproductive endocrine system thus may be evaluated by quantitation of serum DHAS.

Adolescent↗