Growth Hormone Secretion In Boys Research Articles

The role of estrogen in bone growth and formation: changes at puberty

The role of estrogen in bone growth and formation: changes at puberty Divya Singh1, Sabyasachi Sanyal2, Naibedya Chattopadhyay11Division of Endocrinology, 2Division of Drug Target Discovery and Development, Central Drug Research Institute (Council of Scientific and Industrial Research), Lucknow, Uttar Pradesh, IndiaAbstract: A high peak bone mass (PBM) at skeletal maturity is a good predictor for lower rate of fracture risks in later life. Growth during puberty contributes significantly to PBM achievement in women and men. The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis has a critical role in pubertal bone growth. There is an increase in GH and IGF-1 levels during puberty; thus, it is assumed that sex steroids contribute to higher GH/IGF-1 action during growth. Recent studies indicate that estrogen increases GH secretion in boys and girls, and the major effect of testosterone on GH secretion is via aromatization to estrogen. Estrogen is pivotal for epiphyseal fusion in young men and women. From studies of individuals with a mutated aromatase gene and a case study of male patient with defective estrogen receptor-alpha (ER-α), it is clear that estrogen is indispensable for normal pubertal growth and growth plate fusion. ER-α and estrogen receptor-beta (ER-β) have been localized in growth plate and bone. ER knockout studies have shown that ER-α-/- female mice have reduced linear appendicular growth, while ER-β-/- mice have increased appendicular growth. No such effect is seen in ER-β-/- males; however, repressed growth is seen in ER-α-/- males, resulting in shorter long bones. Thus, ER-β represses longitudinal bone growth in female mice, while it has no function in the regulation of longitudinal bone growth in male mice. These findings indicate that estrogen plays a critical role in skeletal physiology of males as well as females.Keywords: peak bone mass, puberty, estrogen, growth plate

Estrogen receptor blockade with tamoxifen diminishes growth hormone secretion in boys: evidence for a stimulatory role of endogenous estrogens during male adolescence

Estrogen receptor blockade with tamoxifen diminishes growth hormone secretion in boys: evidence for a stimulatory role of endogenous estrogens during male adolescence

Estrogen receptor blockade with tamoxifen diminishes growth hormone secretion in boys: evidence for a stimulatory role of endogenous estrogens during male adolescence.

The increase in GH production during the male adolescent growth spurt has been attributed to both androgen and estrogen receptor-mediated processes. To evaluate the role of endogenous estrogens in the control of GH secretion, we administered the estrogen receptor antagonist tamoxifen to 10 late pubertal males. Blood samples were obtained for GH determination at 10-min intervals on 2 occasions during the last 24 h of a 4-day course of either tamoxifen or placebo. Waveform-specific, multiple parameter deconvolution analysis was employed to assess GH secretory and elimination dynamics. Estrogen receptor blockade resulted in a significant (P < 0.05) diminution in mean 24-h serum GH concentrations, from 3.9 +/- 1.0 (placebo; mean +/- SEM) to 2.7 +/- 0.6 micrograms/L (tamoxifen). This was associated with a significant (P < 0.01) decline in the GH production rate [237 +/- 55 vs. 155 +/- 33 micrograms/L GH distribution volume (Lv).24 h]. Furthermore, this reduction in GH secretion was the result of significant decreases in both the maximal GH secretory rate (0.46 +/- 0.08 vs. 0.34 +/- 0.06 microgram/Lv.min; P < 0.01) and, to a smaller degree, GH secretory burst number (16 +/- 1 vs. 14 +/- 1/24 h; P < 0.05). There was also a trend toward reduced mass of GH secreted per burst (13.3 +/- 2.5 vs. 10.3 +/- 2.0 micrograms/Lv; P = 0.06). No significant alterations in either GH elimination t1/2 or GH secretory burst half-duration were observed during estrogen receptor antagonism. Tamoxifen treatment was associated with a significant (P < 0.05) decrease in plasma insulin-like growth factor-I concentrations. However, total and free testosterone, 17 beta-estradiol, insulin-like growth factor-binding protein-3, and pooled 24-h LH concentrations were not significantly changed by short term blockade of estrogen action. We postulate that endogenous estrogens play a facilitatory role in neuroendocrine control of the somatotropic axis during puberty in boys. Tamoxifen blocks this estrogen-dependent stimulation of GH secretion without altering the hormone elimination t1/2. Furthermore, we speculate that any stimulatory role of androgens on GH secretion is exerted primarily through the estrogen receptor after aromatization.

The effect of testosterone therapy on spontaneous growth hormone secretion in boys with constitutional delay.

Testosterone treatment is known to improve growth hormone (GH) secretion in boys with constitutional delay (CD). To determine whether spontaneous GH secretion is normal after treatment, we assessed GH secretion before and after a four- to five-month course of testosterone enanthate in eight adolescents with CD. Before testosterone therapy, the mean (+/- 1 SD) 24-hour integrated concentration of GH (IC-GH) by constant blood withdrawal technique was 1.7 +/- 1.0 micrograms/L (normal range for age, 3.2 to 11.5 micrograms/L), and the IC-testosterone was 1.8 +/- 2.7 nmol/L. Two patients restudied during treatment had normal IC-GH values. After testosterone treatment, the mean IC-GH of the entire group was 3.3 +/- 2.6 micrograms/L, and the IC-testosterone was 6.5 +/- 5.3 nmol/L. Five of eight patients had IC-GH values that were again subnormal. A subnormal IC-GH associated with CD may persist after testosterone therapy is discontinued. Deficiency of spontaneous GH secretion may contribute to short stature and slower growth rates in this patient group. Whether GH therapy in these patients would have a beneficial effect on final height is unknown.

The effect of mazindol on growth hormone secretion in boys with Duchenne muscular dystrophy.

Mazindol has been reported to improve muscle function in Duchenne muscular dystrophy (DMD) by virtue of its growth hormone (GH) suppression. The effects were studied on GH secretion (in response to growth hormone releasing factor and sleep) of mazindol 2 mg daily for 3 months in five boys with DMD. No consistent change was found following mazindol therapy. Adverse effects were noted in all the boys which may preclude long term use of mazindol in DMD.

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.

We tested the hypothesis that selective beta 1-adrenergic blockade will enhance growth hormone (GH) secretion in boys with constitutional delay of growth in response to both exogenously administered growth hormone-releasing hormone as well as to endogenous GH-releasing hormone pulsations. The study group comprised eight healthy, short, prepubertal boys ranging from 7 2/12 to 15 0/12 yr old with bone ages delayed 15 to 42 months. All had demonstrated GH levels of greater than 10 ng/ml following a pharmacologic or physiologic stimulus. During two consecutive nights, blood samples were withdrawn every 20 min for GH determination between 2000 and 0800 h. Immediately after each 0800 h blood withdrawal, 1 microgram/kg of GH-releasing hormone (1-40)-OH was administered intravenously to each subject and blood was withdrawn every 15 min for an additional 2 h. During the day before the second overnight sampling period each subject received atenolol, 25 mg orally, at 1030 and 1600 h to induce beta-adrenergic blockage. The six subjects in whom beta-adrenergic blockade could be documented had enhanced GH release after GH-releasing hormone administration on the atenolol treatment day both in terms of higher peak GH levels achieved (p less than 0.05) as well as greater total GH secretion (3916 +/- 701 versus 5624 +/- 986 ng/ml.min, p less than 0.01). In contrast, there were no differences in endogenous, unstimulated nocturnal GH pulse characteristics between study and control days.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of puberty on growth hormone secretion in boys with short stature and delayed adolescence.

Summary The effect of puberty on pituitary function, with particular reference to growth hormone (GH) and luteinising hormone (LH) secretion, was assessed in eight boys presenting with short stature and delayed onset of puberty. Six patients underwent spontaneous puberty, one was treated with testosterone, and the eighth was treated with human chorionic gonadotrophin (HCG). In the prepubertal state the peak serum GH levels achieved in response to insulin induced hypoglycaemia ranged from 0.4 to 2.4 ng/ml (mean 1.32 ± 0.66 SD) and were similar to levels observed in children with organic hypopituitarism. After the onset of spontaneous or induced puberty, there was a rapid increase in growth rate associated with a significantly increased peak serum GH response (P <.01) to hypoglycaemia ranging from 7.0 to 16 ng/ml with a mean of 9.6 ± 2.6 SD. These studies indicate that short stature and delayed puberty are not always “physiological” but may represent a state of reversible, functional hypopituitarism and that repeated measurements of the serum GH response to insulin hypoglycaemia after testosterone priming may be helpful in differentiating these children from those with other forms of hypopituitarism.