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Papers by alan Rogol

Endocrine Reviews, Dec 7, 2004

Body composition exhibits marked variations across the early human lifetime. The precise physiolo... more Body composition exhibits marked variations across the early human lifetime. The precise physiological mechanisms that drive such developmental adaptations are difficult to establish. This clinical challenge reflects an array of potentially confounding factors, such as marked intersubject differences in tissue compartments; the incremental nature of longitudinal intrasubject variations in body composition; technical limitations in quantitating the unobserved mass of mineral, fat, water, and muscle ad seriatim; and the multifold contributions of genetic, dietary, environmental, hormonal, nutritional, and behavioral signals to physical and sexual maturation. From an endocrine perspective (reviewed here), gonadal sex steroids and GH/IGF-I constitute prime determinants of evolving body composition. The present critical review examines hormonal regulation of body composition in infancy, childhood, and puberty. (Endocrine Reviews 26: 114-146, 2005) I. Timing and Tempo of Normal Human Growth A. Linear growth and body weight B. Body composition in childhood and puberty II. Measurement of Body Composition A. Body mass index B. Two-compartment models C. Four-compartment models D. Two-and three-compartment models E. Fat topography F. Clinic and field methods III. Sex-Steroid and GH Interactions on Target Tissues in Puberty A. Overview B. Actions of androgen, estrogen, GH, and IGF-I on bone C. Adiposity and sex-steroid hormones D. Adiposity and GH/IGF-I E. Control of muscle by sex steroids and GH/IGF-I IV. Energy Expenditure in Puberty V. Summary I. Timing and Tempo of Normal Human Growth A. Linear growth and body weight A UXOLOGY [Gk. auxesis, to increase or grow; logos, study] is the scientific analysis of physical growth and development. Growth is a complex process that is sustained throughout in utero development, infancy, childhood, puberty, and early adulthood. Dynamic control of growth is endowed by age-and gender-dependent interactions among key genetic, environmental, dietary, socioeconomic, developmental, behavioral, nutritional, metabolic, biochemical, and hormonal factors. Thus, normative data must be developed from age-specific, gender-matched, and genetically comparable healthy populations. Although normative isobars are widely used for comparisons of static height, the endocrinologist and pediatrician should also evaluate the velocity of linear growth velocity (annual increment in height), chronological and apparent biological age, pubertal status, family history, and psychosocial adjustment. From a clinical perspective, biological age is often assessed indirectly as radiographic bone age. The velocity of in utero linear growth is maximal at about 18 wk of gestational age in the human. At this time, the fetus grows four times more rapidly than at any time postnatally. Increases in body weight follow a similar temporal pattern, except that the zenith occurs at about 34 wk. The growth rate declines sharply during the last weeks of gestation. The maternal-placental environment dictates the infant's birth weight more than the fetal genotype (1). In the newborn, height velocity adjusts toward the genetically predicted trajectory. Linear growth averages approximately 25 cm in the

Frontiers in Endocrinology, 2020

Emotional deprivation can lead to growth faltering of infants and children. The mechanism(s) invo... more Emotional deprivation can lead to growth faltering of infants and children. The mechanism(s) involved differ in that for infants, the major metabolic problem is inadequate energy intake for growth. In young children, it is likely that the emotional deprivation causes a syndrome not only of growth faltering, but with bizarre behaviors, especially with regard to food: hoarding, gorging and vomiting, hyperphagia, drinking from the toilet, and eating from garbage pails. Other disturbed behaviors include, poor sleep, night wanderings, and pain agnosia. The pathophysiology appears to be reversible hypopituitarism, at least for the growth hormone and hypothalamic-pituitary-adrenal axes. The review begins with an historical perspective concerning stress, children and growth and then moves to the issue of hospitalism, where young infants failed to thrive (and died) due to inadequate stimulation and energy intake. Refeeding programs at the end of World Wars I and II noted that some children did not thrive despite an adequate energy intake. It appeared that in addition taking care of their emotional needs permitted super-physiologic (catch-up) growth. Next came the first notions from clinical investigation that hypopituitarism might be the mechanism of growth faltering. Studies that address this mechanism from a number of observational and clinical research studies are reviewed in depth to show that the hypopituitarism was relieved upon removal from the deprivational environment and occurred much too quickly to be due to adequate energy alone. These findings are then compared to those from malnourished children and adoptees from emerging countries, especially those from orphanages where their psychosocial needs were unmet despite adequate caloric intake. Together, these various conditions define one aspect of the field of psychoneuroendocrinology.

Frontiers in Endocrinology

Since antiquity Man has been fascinated by the variations in human (and animal) growth. Stories a... more Since antiquity Man has been fascinated by the variations in human (and animal) growth. Stories and art abound about giants and little people. Modern genetics have solved some of etiologies at both extremes of growth. Serious study began with the pathophysiology of acromegaly followed by early attempts at treatment culminating in modern endoscopic surgery and multiple pharmacologic agents. Virtually at the same time experiments with the removal of the pituitary from laboratory animals noted the slowing or stopping of linear growth and then over a few decades the extraction and purification of a protein within the anterior pituitary that restored, partially or in full, the animal’s growth. Human growth hormone was purified decades after those from large animals and it was noted that it was species specific, that is, only primate growth hormone was metabolically active in primates. That was quite unlike the beef and pork insulins which revolutionized the care of children with diabetes...

Journal of the Endocrine Society, 2021

Context: There is no consensus on the effect of recombinant human growth hormone (rhGH) therapy o... more Context: There is no consensus on the effect of recombinant human growth hormone (rhGH) therapy on skeletal maturation in children despite the current practice of annual monitoring of skeletal maturation with bone age in children on rhGH therapy. Aims: To investigate the effects of long-term rhGH therapy on skeletal age in children and explore the accuracy of bone age predicted adult height (BAPAH) at different ages based on 13 years of longitudinal data. Methods: A retrospective longitudinal study of 71 subjects aged 2-18 years, mean 9.9 ± 3.8y, treated with rhGH for non-syndromic short stature for a duration of 2-14y, mean, 5.5 ± 2.6y. Subjects with syndromic short stature and systemic illnesses such as renal failure were excluded. Results: Bone age minus chronological age (BA-CA) did not differ significantly between baseline and the end of rhGH therapy (-1.05 ± 1.42 vs -0.69 ± 1.63, p=0.09). Piece-wise regression however showed a quantifiable catch-up phenomenon in BA of 1.6 mont...

Endocrinologia Japonica, 1987

Pediatric Research, 1988

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Journal of Clinical Investigation, 1982

old woman with Turner's syndrome presented with signs and symptoms of acromegaly. The serum growt... more old woman with Turner's syndrome presented with signs and symptoms of acromegaly. The serum growth hormone (GH) (95±9.4 ng/ ml; mean±SEM) and somatomedin C (11 U/ml) levels were elevated, and an increase in GH levels after glucose instead of normal suppression, increase after thyrotropin-releasing hormone (TRH) administration instead of no change, and decrease after dopamine administration instead of stimulation were observed. The pituitary fossa volume was greater than normal (1,440 mm3) and the presence of a pituitary tumor was assumed. After tissue removal at transsphenoidal surgery, histological study revealed somatotroph hyperplasia rather than a discrete adenoma. Postoperatively, she remained clinically acromegalic and continued to show increased GH and somatomedin levels. A search was made for ectopic source of a growth hormonereleasing factor (GRF). Computer tomographic scan revealed a 5-cm Diam tumor in the tail of the pancreas. Following removal of this tumor, serum GH fell from 70 to 3 ng/ml over 2 h, and remained low for the subsequent 5 mo. Serum somatomedin C levels fell from 7.2 to normal by 6 wk postoperatively. There were no longer paradoxical GH responses to glucose, TRH, and dopamine. Both the medium that held the tumor cells at surgery and extracts of the tumor contained a peptide with GRF activity. The GRF contained in the tumor extract coeluted on Sephadex Dr.

Endocrine Reviews, 2020

We provide an in-depth review of the role of androgens in male maturation and development, from t... more We provide an in-depth review of the role of androgens in male maturation and development, from the fetal stage through adolescence into emerging adulthood, and discuss the treatment of disorders of androgen production throughout these time periods. Testosterone, the primary androgen produced by males, has both anabolic and androgenic effects. Androgen exposure induces virilization and anabolic body composition changes during fetal development, influences growth and virilization during infancy, and stimulates development of secondary sexual characteristics, growth acceleration, bone mass accrual, and alterations of body composition during puberty.Disorders of androgen production may be subdivided into hypo- or hypergonadotropic hypogonadism. Hypogonadotropic hypogonadism may be either congenital or acquired (resulting from cranial radiation, trauma, or less common causes). Hypergonadotropic hypogonadism occurs in males with Klinefelter syndrome and may occur in response to pelvic ra...

The Journal of Pediatrics, Jul 1, 1997

GHR locus may play a role in the cause of idiopathic short stature (ISS) by impairing growth-horm... more GHR locus may play a role in the cause of idiopathic short stature (ISS) by impairing growth-hormone (GH) receptor (GHR) function. At one extreme, mutations that nullify the function of the GH receptor are linked to complete GH insensitivity syndrome, or Laron syndrome, and we hypothesized that less-disruptive mutations could contribute to partial GH insensitivity syndrome. Low levels of GH binding protein may indicate mutations in the extracellular domain of the receptor, and by focusing on 14 children with ISS who had low GH binding protein and insulin-like growth factor I levels, we found three heterozygotes and one compound heterozygote for mutations in the extracellular domain of the receptor. We have since extended our study to a broader spectrum of patients, adding 76 patients with ISS who were treated with GH in a phase II study of the safety and efficacy of recombinant human GH in ISS and also adding 10 patients who were ascertained as having ISS by pediatric endocrinologists in private practice. The GHR gene has thus been analyzed in 100 patients with ISS, eight of whom were found to carry mutations: four in our original study and four with normal or elevated levels of GH binding protein. The latter group

Hormone Research in Paediatrics, 2019

The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagn... more The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some ...

Journal of Applied Physiology, 1992

The effects of intensity of run training on the pulsatile release of growth hormone (GH) were inv... more The effects of intensity of run training on the pulsatile release of growth hormone (GH) were investigated in 21 eumenorrheic untrained women. The O2 consumption (VO2) at the lactate threshold (LT); fixed blood lactate concentrations (FBLC) of 2.0, 2.5, and 4.0 mM; peak VO2; maximal VO2; body composition; and pulsatile release of GH were measured. Subjects in both the at-lactate threshold (/LT, n = 9) and above-lactate threshold (greater than LT, n = 7) training groups increased VO2 at LT and FBLC of 2.0, 2.5, and 4.0 mM and VO2max after 1 yr of run training. However, the increase observed in the greater than LT group was greater than that in the /LT group (P less than 0.05). No change was observed for the control group (n = 5). No among- or within-group differences were observed for body weight, although trends for reductions in percent body fat (P less than 0.06) and fat weight (P less than 0.15) were observed in the greater than LT group, and both training groups significantly in...

Pediatric Research, 2000

* Assay run in limited series, n ϭ 9. Data shown as mean Ϯ SEM with ranges in parentheses. IF is ... more * Assay run in limited series, n ϭ 9. Data shown as mean Ϯ SEM with ranges in parentheses. IF is the immunofunctional GH assay. All concentrations represent the average of at least six samples per subject.

Pediatric Research, 1990

Overnight growth hormone (GH) concentrations obtained by frequent venous sampling of 20 healthy, ... more Overnight growth hormone (GH) concentrations obtained by frequent venous sampling of 20 healthy, short prepubertal boys were evaluated using the objective pulse detection algorithm, CLUSTER. The resulting pulsatile characteristics were compared with those of I l healthy prepubertal bop of normal stature and with those of nine prepubertal children with documented GH deficiency. Although no significant differences of pulsatile GH

Pediatric Research, 1984

We examined and made hormonal measurements at 6 month intervals in 20 normal boys (M) and 15 girl... more We examined and made hormonal measurements at 6 month intervals in 20 normal boys (M) and 15 girls (F) during a longitudinal study of puberty. Initial detectability of Band I-LH, measured in highly sensitive assay systems, was related to chronologic (CA) and skeletal age (BA), pubertal stage and sex steroid levels. In prepuberty, the detectability of B-LH was similar in both sexes (M-27%,F-35%), but differed in I-LH (M-79%,F-40%; ~2=10.026,p<.002). In pubertal stage 11, detectability of both B-LH (M-91%; ,F-48%;g=18. 701 ,p<. 001) and I-LH (M-89%,F-49%;x2= 21.224,p<.001) differed. In contrast to measurability of I-LH in M at younger age and lower T levels than B-LH, no such difference existed in F when age, pubertal stage, E2 or FSH levels were considered. BA (11.2 vs 9.9,p(.02), but not CA, and pubertal stage (2.2 vs 1.4,p<.005) were significantly later in F than M at the earliest I-LH, but not B-LH, above assay sensitivity. In conclusion: (1) Prepubertal detectability of I-LH was more frequent in M than in F; (2) although B-LH tended to be unmeasurable in Stage I, less than 50% of Stage I1 F had either Bor I-LH found, in contrast to 90% of M; (3) in view of discordant Band I-LH pulses reported in adults, the detectable I-LH potency estimates in immature M must be reevaluated as to alphasubunit or other assay interference, as well as to the problems of use of multiclonal antisera and impure standards.

Pediatric Research, 1993

Aims: to study the growth of children with liver disease before and after LT. Methods: longitudin... more Aims: to study the growth of children with liver disease before and after LT. Methods: longitudinal study (LS): 16 infants (9 M. 7 F); age 0.73 to 2.38 years (x 1.39) at LT: mean height (Ht) SDS at LT:-2.02 (SO 1.25). Post-LT medication: cyclosporine in tapering doses; prednisone, by dally regimen (DP) for the first 6-12 months. with tapering doses depending on cltn tcal course. then on alternate day regimen (ADP). Cross-sectional st ndy (CSS): 95 children (55 M. 40 F) aged 0.17 to 14.88 (x 3.83). observed before LT. after LT on DP.