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Biomedical subjects

A W Root

Publications and source records attributed to A W Root.

At least 109 records · Page 6Linked to original sources

LH and FSH levels in urine and serum of prepubertal and pubertal children receiving a 3 hour infusion of LH-RH.

LH-RH was administered to 17 normal prepubertal and 14 pubertal children as well as to 6 GH deficient prepubertal patients. Urinary immunoreactive LH and FSH were measured in acetone extracts of 3 h collections prior to, during, and immediately after a 3 h infusion of 100 mug LH-RH. Peak LH excretion in response to LH-RH was higher in pubertal than prepubertal children. Girls excreted larger quantities of FSH after LH-RH than did boys. Serum LH and FSH increments evoked by LH-RH correlated significantly (P less than 0.01) with peak urinary gonadotropin excretion. These data suggest that measurement of urinary immunoreactive LH and FSH prior to and after LH-RH administration is clinically useful in evaluation of the reproductive endocrine system of young children and of individuals with low basal levels of gonadotropin.

Adolescent↗

Urinary excretion of immunoreactive gonadotropin-releasing hormone-like material in prepubertal and pubertal children.

A urinary product with immunological similarity to Gn-RH has been quantified by radioimmunoassay. The i-Gn-RH-like material apparently has a (partial) structure consistent with the 5 leads to 9 amino acid sequence of hypothalamic Gn-RH. It inhibits the binding of 125I-Gn-RH to anti Gn-RH serum in a manner parallel to synthetic standard, is absorbed by incubation with anti Gn-RH serum, and comigrates with synthetic Gn-RH on Sephadex column chromatography. The concentration of i-Gn-RH-like material is maximal in pubertal males. The total urinary excretion of this substance is two-fold greater in pubertal subjects of both sexes than in prepubertal children. There is no diurnal variation in the excretion of this material. There are significant positive correlations between the urinary content of iGN-RH-like material and LH and FSH. The site of origin, structure and physiological significance of this immunological product remain to be elucidated.

Adolescent↗

Simultaneous radioimmunoassay of thyrotropin and thyroxine in human serum.

The importance of early diagnois and treatment of congenital hypothyroidism has been well established, and several screening programs have been undertaken to detect neonates with this disorder by measurement of concentrations of thyrotropin or thyroxine in the serum. However, measurement of either hormone alone may fail to identify all affected patients. Accordingly, we have established a simultaneous double-antibody, dual-isotope radioimmunoassay for both. Sensitivity, slope, analytical recovery, and precision characteristics of the simultaneous assay do not differ from those of each assay performed separately. Values for the two analyses in the single and simultaneous assays correlate well (r = 0.951 for thyroxine, 0.983 for thyrotropin). This assay system permits determination of both hormones within 72 h after specimen collection and thus should allow more rapid evaluation, diagnosis, and treatment of infants with congenital hypothyroidism.

Buffers↗

Effect of infusion of gonadotropin releasing hormone upon plasma concentrations of sex hormones in prepubertal and pubertal males.

Plasma testosterone (T), dihydrotestosterone (DHT), 17-hydroxyprogesterone (17OHP), androstenedione (A), estradiol (E2), and dehydroepiandrosterone sulfate (DHAS) were measured by radioimmunoassay after celite chromatography prior to and after a 3-hour infusion of the synthetic gonadotropin releasing factor, GnRH, in normal prepubertal and pubertal boys. Plasma T levels rose (p less than 0.001) in the pubertal but not prepubertal boys. 17OHP concentrations increased in those boys who had an increment of T. A, DHT, E2 or DHAS levels did not increase after GnRH. Basal levels of T, DHT, A and DHAS correlated with the peak and mean serum LH levels attained during the GnRH infusion. These data confirm the greater Leydig cell responsivity to transient rises of endogenous gonadotropin in pubertal males and also suggest that there may be a relationship between adrenal androgen production and maturation of the hypothalamic-pituitary-gonadal system.

Age Factors↗

Evaluation and management of the child with delayed pubertal development.

The physical and hormonal changes of puberty are presented and the wide range of ages at which the pubertal process may begin is emphasized. The great variability in the timing of onset of adolescence, its rate of progression, and the age of completion are detailed. The causes of delayed adolescence in males and females are considered. The most common form of delayed adolescent development is termed constitutional delay in growth and development, which may occur sporadically, or may be the familial pattern of growth and development or may reflect a suboptimal nutritional environment. The evaluation of such children, including appropriate historical review, physical examination, and laboratory assessment, is outlined. In most patients with constitutional delay in growth and development, strong reassurance is sufficient therapy. In other subjects, treatment with androgens (boys) or estrogens (girls) may be indicated. In patients with primary systemic diseases accociated with delayed maturation, specific treatment which eradicates the illness will often be followed by resumption of growth and development. In subjects with primary disorders of the hypothalamus, pituitary, or gonads, replacement therapy with androgens or estrogens is indicated. If gonadal function is intact, these patients may eventually become fertile with appropriate use of hypothalamic and/or pituitary hormones.

Adolescent↗

Recent advances in calcium metabolism. I. Mechanisms of calcium homeostasis.

Within recent years newly acquired knowledge has provided a clearer understanding of some aspects of the complex mechanisms that collectively maintain calcium homeostasis within body fluids and it is our intent to define current concepts of the interrelationship of these various factors to the end that fuller understanding may be available concerning the maintenance of calcuim homeostasis in health as well as features which result in its disruption and the consequent effects of imbalances of calcium in various disease states. In this first section dealing with the physiologic state, there are included descriptions of: (1) the metabolism of vitamin D, the synthesis of its active metabolites, 25 OHD3 and1.25(OH)2D3, and the metabolic actions of the active vitamin D metabolite and analogues upon gastrointestinal, bone, and kidney functions; (2) the synthesis, secretion, and metabolic activity of parathyroid hormone and the difficulties with the radioimmunoassay of PTH related to the number of PTH-like peptides in the circulation; and (3) the chemistry, metabolism, and biologic activities of calcitonin, a hypocalcemic principle derived from the parafollicular cells of the thyroid gland. It is emphasized that under normal circumstances these humoral mechanisms act in an integrated manner to maintain serum concentrations of total and ionized calcium within narrowly defined limits.

Adolescent↗

Parathyroid function in uremic children during periods of renal insufficiency, hemodialysis, and transplantation.

Function of the parathyroid gland was evaluated in children with renal insufficiency prior to and after imitation of hemodialysis, and again following renal transplantation. Serum levels of immunoreactive parathyroid hormone responded appropriately to increases or decreases of serum calcium concentrations in the three groups. Functional and histologic studies in the children with renal insufficiency demonstrated the cause of their elevated circulating levels of iPTH to be diffuse parathyroid hyperplasia. During hemodialysis, the serum concentration of calcium rose and that of iPTH decreased, when the calcium gradient between the dialysate and the blood favored movement of calcium into the body. During treatment with prednisolone (20 mg/kg intravenously) for reversal of renal transplant rejection, the serum concentration of calcium decreased and that of iPTH increased. These observations suggest that autonomy of the parathyroid gland rarely occurs in children with renal insufficiency, and that hemodialysis using a dialysate with a high concentration of calcium might assist in retarding the progression of renal osteodystrophy. Furthermore, if hyperparathyroidism contributes in part to growth failure in children with chronic renal disease, steroid-induced changes in cirulating iPTH following renal transplantation may inhibit growth.

Calcium↗

Recent advances in calcium metabolism. II. Disorders of calcium homeostasis.

Abnormalities of calcium and mineral metabolism are described in relation to the differential diagnosis, clinical characteristics, diagnostic procedures, and treatment of infants and children with hypocalcemia, hypercalcemia, rickets, chronic renal insufficiency, and other disorders of calcium metabolism. Understanding of the basic pathogenesis of each abnormality of calcium homeostasis is essential for the rational management of affected patients.

Adolescent↗

The response of pituitary gonadotropes to a constant infusion of luteinizing hormone-releasing hormone (LHRH) in normal prepubertal and pubertal children and in children with abnormalities of sexual development.

The pattern of LHRH-evoked release of LH and FSH by pituitary gonadotrophs and the concomitant gonadal steroid secretion were studied in 28 pubertal and 16 prepubertal children. LHRH was administered at doses of 100 mug and 10 mug by a constant-infusion pump over 3 hours following a 2-hour control period. Gonadotropin concentrations were measured at 15-minutes intervals. Mean LH concentrations rose from 2.0 +/- 0.4 (SE) mIU/ml (IRP-2-hMG) to 6.2 +/- 0.9 (P less than .001) in normal prepubertal and from 5.8 +/- 0.9 to 28.0 +/- 3.6 (P less than .001) in normal pubertal children. The peak rise of LH, the mean level attained during the LHRH infusion, and the area under the time-response curve were greater (P less than .001) in pubertal than prepubertal children. The serum LH rise had two components in pubertal children in contrast to a single-phased increase in prepubertal children. Pulsatile release of LH was demonstrated during the basal period in pubertal children and during the LHRH infusion in both groups. FSH release was greater in girls than boys at both stages of pubertal development. A 10 mug LHRH infusion released less LH than did 100 mug in the pubertal children, but more than in prepubertal children. In pubertal boys, plasma testosterone rose (P less than .001) from 222 +/- 45 ng/dl in the control period to 301 +/- 59 following 100 mug LHRH. There was no change in plasma testosterone in the prepubertal boys after 100 mug LHRH or in the pubertal boys following 10 mug LHRH. Plasma estradiol did not rise in girls of either maturity group. In children with hypogonadotropic hypogonadism and structural abnormalities of the hypothalamic-pituitary region, there was no LHRH-evoked gonadotropin release. In 2 agonadal girls, the secretion of LH and FSH was greatly exaggerated. The 3-hour LHRH infusion evoked a maturity-related pituitary LH release and a sex-specific FSH release; a 2-phased pattern of LH secretion was present in pubertal but not in prepubertal children; pulsatile LH release was evoked by the LHRH infusion in prepubertal children.

Adolescent↗

Effects of new multi-site hormone blockers on the fertility of male rats.

The effects on the fertility of adult male rats of six new synthetic steroids: I, 3-cyano-5alpha-androst-1-en-17-one; II, the 17beta-acetate form of I; III, 17beta-hydroxy-5beta-cyano-androstan-3-one; IV, 6-methylpregnenolone; V, 17beta-hydroxy-17alpha-ethynyl-5beta-cyano-19-norandrostan-3-one; and VI, 19-norspiroxenone (oestr-4-en-3-one-spiro-17alpha-2'-[tetrahydrofuran]) have been tested. After 6 weeks of treatment with daily doses of 5 mg (I, II, III), 15 mg (IV) or 10 mg (V, VI) only steroid VI blocked the completion of spermatogenesis and reduced the number of foetuses sired in at least five females/male. Steroid VI also diminished seminal vesicular, prostatic, testicular and epididymal weights. It inhibited the testicular enzymes, 3beta-hydroxysteroid dehydrogenase-delta4-5-3-oxosteroid isomerase system, 17alpha-hydroxylase, and C17-20 lyase markedly, but did not affect the adrenal dehydrogenase-isomerase system. It depressed, strikingly, testicular and serum levels of testosterone and 5alpha-dihydrotestosterone and reduced pituitary and serum levels of FSH and LH. Although marked depression of target organ weights also occurred with steroids II, IV and V, and reduction of androgen levels and LH in the circulation with III, IV and V, only VI was a potent blocker of male fertility with the exception of a slight block of the siring of viable foetuses by steroids IV and V. The major difference in site of action of steroid VI from the others was the depression of pituitary and serum levels of FSH along with a marked diminution of testicular content of both testosterone and 5alpha-dihydrotestosterone. 19-Norspiroxenone in the rat is a potent anti-oestrogen without inherent oestrogenicity and is anti-uterotrophic. Thus, VI may affect male fertility by virtue of its potent anti-oestrogenic action in the hypothalamus or testis.

Androstanes↗

Renal wastage of insulin in children with diabetes mellitus.

In normal human beings the percentage of serum insulin excreted in the urine is constant over a wide range of values. The quantity of immunoreactive insulin found in the urine is believed to reflect the level of free insulin in the serum. Immunoreactive insulin was measured in the urine of nondiabetic children and diabetic children receiving exogenous insulin. Children with diabetes mellitus excreted greater amounts of immunoreactive insulin (18.5+/-8 muU./mg. creatinine) than did nondiabetic children (11.9+/-5 muU./mg. creatinine). This difference was statistically significant (p less than 0.0005). Children with "poor glycemic control" excreted a greater portion of their administered insulin dose than did those with "good control." The renal wastage of insulin correlated (r=0.94) with the duration of insulin treatment but not with the quantity administered. Antibody binding of serum insulin may explain in part these observations, but an acquired defect in the renal tubular reabsorption of insulin may also exist. Modifications in the management of diabetes that reduce the renal wastage of insulin may improve the metabolic stability of children with "poor diabetic control."

Adolescent↗

Growth hormone and prolactin in the fetus.

Growth hormone is released from pituitary glands maintained in tissue culture as early as 5 weeks after conception. It has been identified in the fetal anterior pituitary gland by immunologic and biologic techniques between 7 and 15 weeks of gestation. Immunoreactive pituitary GH levels increase rapidly between 10 and 14 weeks of gestation to maximal levels at 30-34 weeks. Serum GH levels are detectable by 10-weeks postconception and reach maximal values at 20-24 weeks declining thereafter until term. Pospartum GH concentrations decline over several weeks to lower values, GH levels remaining higher in preterm than in term infants. The biologic role of pituitary GH in the fetus is unknown. Although birth-weights and lengths are reported to be normal in infants with anencephaly, aplasia, or hypoplasia of the pituitary gland and in isolated deficiency of growth hormone, in whom pituitary and serum GH levels are low, careful inspection of large series of such infants reveals that their birthweights may indeed be low and that cell numbers in many organs may be subnormal. In experimental animals prenatal administration of GH increases maternal weight and gestational length. Reported effects on neuronal growth and adult intelligence of animals treated prenatally may reflect these phenomena rather than a direct transplacental effect of GH. Prolactin is also elaborated by the pituitary gland of very young human fetuses. It has been identified immunologically by 10-weeks gestation and biologically at 18 weeks. Pituitary content of immunoreactive prolactin remains low until 16.5-weeks gestation and then increases steadily until term. The plasma concentration of prolactin is low until 30-weeks gestation and increases thereafter until term. In anencephalic fetuses prolactin levels are normal and respond to appropriate stimuli. Very high concentrations of (possibly fetal) prolactin are found in the amniotic fluid. The role of prolactin in the fetus is also unknown. It has been suggested that prolactin may be important for growth of the fetal adrenal cortex and/or for suppression of the immune response during pregnancy. It is apparent that a great deal of additional work is necessary before the importance of either growth hormone of prolactin for normal fetal growth and development will be known.

Animals↗

Hormonal changes of adolescence.

Pubescence is characterized by many physical, emotional, and hormonal changes. The hypothalamic-pituitary-gonadal system is maintained in a dormant state (with a low level of activity) during prepubertal years by higher central nervous system inhibition. With the onset of adolescence, the reproductive endocrine system becomes increasingly active. The attainment of sexual maturity in terms of secondary sexual characteristics, the production of spermatozoa in the male, and the cyclical female pattern with release of ova are end-points of the developmental process.

Adolescent↗

Pituitary hormone secretion in the genectically male rat pseudohermaphrodite.

Pituitary content or concentration of follicle-stimulating hormone (FSH), prolactin and growth hormone in the genetically androgen insensitive male rat pseudohermaphrodite is intermediate between normal male and female rats, while pituitary luteinizing hormone (LH) concentration and serum FSH levels are the same as in the normal male. The concentration of serum LH, prolactin and growth hormone indicated no sexual dimorphism. Although the pseudohermaphrodite is genetically male with a female phenotype, our results suggest some degree of masculinization of the hypothalamic-pituitary system.

Animals↗