Atenolol Enhances Growth Hormone Release to Exogenous Growth Hormone-Releasing Hormone but Fails to Alter Spontaneous Nocturnal Growth Hormone Secretion in Boys with Constitutional Delay of Growth

Martha, Paul M.; Blizzard, Robert M.; Rogol, Alan D.

doi:10.1203/00006450-198804000-00010

Cited by 27 publications

(6 citation statements)

References 25 publications

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“…However, caution is required in interpreting single bolus (exogenous) GHRH stimulation tests, because of varying endogenous somatostatinergic tone (39). In addition, exactly which (if any) individual neurotransmitters play a role in triggering the increased mass of GH released per pulse in the presence of steroid hormones is not known, but clinical data indicate that adrenergic and cholinergic systems can regulate episodic GH release via amplitude-dependent mechanisms in boys with constitutionally delayed puberty (40)(41)(42). Such neurotransmitter pathways, in turn, mediate increased GH secretion via effects on somatostatin and/or GHRH release or action (3,27,28,31,42,43).…”

Section: Discussionmentioning

confidence: 98%

Testosterone and Oxandrolone, a Nonaromatizable Androgen, Specifically Amplify the Mass and Rate of Growth Hormone (GH) Secreted per Burst without Altering GH Secretory Burst Duration or Frequency or the GH Half-Life*

Ulloa‐Aguirre

Blizzard

Garcia-Rubi

et al. 1990

The Journal of Clinical Endocrinology & Metabolism

124

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We investigated the mechanisms by which androgens increase mean circulating GH concentrations in boys. We tested two hypotheses: 1) testosterone increases serum GH concentrations at least in part via an androgen receptor-mediated mechanism, rather than exclusively by way of aromatization to estrogen; 2) androgen augments one or more specific features to GH secretion (secretory burst number, amplitude, and/or duration) and/or prolongs the half-life of GH removal. To examine these hypotheses, prepubertal boys with constitutionally delayed development and/or growth were given injections of testosterone (100 mg monthly; n = 7) or treated with oral oxandrolone, a nonaromatizable androgen (1.25 mg twice daily; n = 5). Pulsatile GH release was studied before and during androgen administration by sampling blood at 20-min intervals for 24 h. The immunoreactive GH time series were subjected to a novel deconvolution technique, which revealed that 1) testosterone and oxandrolone each increased mean (24-h) serum GH concentrations significantly; 2) both androgens augmented the daily endogenous GH secretory rate significantly; 3) increased GH production resulted from a higher mass of GH secreted per burst and a higher maximal rate of GH secretion within each burst; and 4) androgens amplified the magnitude of the nyctohemeral rhythm in the mass (but not frequency) of GH secretory pulses. The observed effects of androgen were specific, since the number and duration of GH secretory bursts and the subject-specific GH half-life were unaltered by androgen treatment. We conclude that androgen acting apart from conversion to estrogen is capable of specifically activating the somatotropic axis via distinct neuroendocrine secretory mechanisms.

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Section: Discussionmentioning

confidence: 98%

Testosterone and Oxandrolone, a Nonaromatizable Androgen, Specifically Amplify the Mass and Rate of Growth Hormone (GH) Secreted per Burst without Altering GH Secretory Burst Duration or Frequency or the GH Half-Life*

Ulloa‐Aguirre

Blizzard

Garcia-Rubi

et al. 1990

The Journal of Clinical Endocrinology & Metabolism

124

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“…Osteoblasts are known targets of Pb toxicity from in vitro studies with ROS 17/2.8 cells, which demonstrated suppression of alkaline phosphatase, type I collagen, and osteocalcin (Long et al 1990). In addition, circulating levels of osteocalcin, which serve as markers of osteoblast activity and regulators of bone formation and remodeling (Ducy et al 1996), are decreased in Pb-intoxicated children (Markowitz et al 1988). The mechanism by which these effects occur remains unclear.…”

mentioning

confidence: 99%

Lead Exposure Inhibits Fracture Healing and Is Associated with Increased Chondrogenesis, Delay in Cartilage Mineralization, and a Decrease in Osteoprogenitor Frequency

Carmouche

Puzas

Zhang

et al. 2005

Environ Health Perspect

120

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Lead exposure continues to be a significant public health problem. In addition to acute toxicity, Pb has an extremely long half-life in bone. Individuals with past exposure develop increased blood Pb levels during periods of high bone turnover or resorption. Pb is known to affect osteoblasts, osteoclasts, and chondrocytes and has been associated with osteoporosis. However, its effects on skeletal repair have not been studied. We exposed C57/B6 mice to various concentrations of Pb acetate in their drinking water to achieve environmentally relevant blood Pb levels, measured by atomic absorption. After exposure for 6 weeks, each mouse underwent closed tibia fracture. Radiographs were followed and histologic analysis was performed at 7, 14, and 21 days. In mice exposed to low Pb concentrations, fracture healing was characterized by a delay in bridging cartilage formation, decreased collagen type II and type X expression at 7 days, a 5-fold increase in cartilage formation at day 14 associated with delayed maturation and calcification, and a persistence of cartilage at day 21. Fibrous nonunions at 21 days were prevalent in mice receiving very high Pb exposures. Pb significantly inhibited ex vivo bone nodule formation but had no effect on osteoclasts isolated from Pb-exposed animals. No significant effects on osteoclast number or activity were observed. We conclude that Pb delays fracture healing at environmentally relevant doses and induces fibrous nonunions at higher doses by inhibiting the progression of endochondral ossification.

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“…High BLLs among children have been associated with lower osteocalcin, a biomarker of osteoblastic (bone forming) activity (Markowitz et al 1988). In rodent models, the direct effects of lead on the epiphyseal growth plate (Pounds et al 1991) are consistent with findings in cross-sectional cohorts of Polish (ages 7–15 years) (Ignasiak et al 2006) and Korean children (ages 5–13 years) (Min et al 2008) of negative associations of BLL with height and a marked reduction in arm and leg length suggesting disruption of long bone epiphyses.…”

Section: Discussionmentioning

confidence: 99%

Peripubertal blood lead levels and growth among Russian boys

Burns

Williams

Lee

et al. 2017

Environment International

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Background Childhood blood lead levels (BLL) have been associated with growth impairment. Objectives We assessed associations of peripubertal BLL with adolescent growth and near adult height in a longitudinal cohort of Russian boys. Methods 481 boys were enrolled at ages 8–9 years and followed annually to age 18. At enrollment, BLL was measured, and height, weight, and pubertal staging were obtained annually during 10 years of follow-up. Mixed effects models were used to assess the associations of BLL with longitudinal age-adjusted World Health Organization Z-scores for height (HT-Z) and body mass index (BMI-Z), and annual height velocity (HV). Interactions between boys’ age and BLL on growth outcomes were evaluated. RESULTS The median (range) BLL was 3.0 (0.5–31.0) μg/dL. At age 18 years, 79% of boys had achieved near adult height (HV <1.0 cm/year), and means (SD) for HT-Z and BMI-Z were 0.15 (0.92) and −0.32 (1.24). Over 10 years of follow-up, after covariate adjustment, boys with higher (≥ 5 μg/dL) BLL compared with lower BLL were shorter (adjusted mean difference in HT-Z = −0.43, 95% CI −0.60, −0.25, p-value <0.001), translating to a 2.5 cm lower height at age 18 years. The decrement in height for boys with higher BLL was most pronounced at 12 to 15 years of age (interaction p=0.03). Boys with higher BLL were leaner (adjusted mean difference in BMI-Z = −0.22, 95% CI: −0.45, 0.01, p=0.06). Conclusions Higher peripubertal BLLs were associated with shorter height through age 18 years, suggesting a persistent effect of lead on linear growth.

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Atenolol Enhances Growth Hormone Release to Exogenous Growth Hormone-Releasing Hormone but Fails to Alter Spontaneous Nocturnal Growth Hormone Secretion in Boys with Constitutional Delay of Growth

Cited by 27 publications

References 25 publications

Testosterone and Oxandrolone, a Nonaromatizable Androgen, Specifically Amplify the Mass and Rate of Growth Hormone (GH) Secreted per Burst without Altering GH Secretory Burst Duration or Frequency or the GH Half-Life*

Testosterone and Oxandrolone, a Nonaromatizable Androgen, Specifically Amplify the Mass and Rate of Growth Hormone (GH) Secreted per Burst without Altering GH Secretory Burst Duration or Frequency or the GH Half-Life*

Lead Exposure Inhibits Fracture Healing and Is Associated with Increased Chondrogenesis, Delay in Cartilage Mineralization, and a Decrease in Osteoprogenitor Frequency

Peripubertal blood lead levels and growth among Russian boys

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