Sexual dimorphism of GH secretion is well-recognized in the rat and characterized by high-amplitude GH pulses occurring at precise 3.3-h intervals and low or undetectable GH troughs in males, whereas females exhibit irregular, more frequent, low-amplitude GH pulses with elevated basal GH levels, no distinct troughs, and slower somatic growth relative to male animals (82). 17^-estradiol administration to gonadectomized and sham-operated adult male rats converts the typical male GH secretory profile to a female-like pattern. Previous work in gonadectomized neonatal male rats has demonstrated reduced GH pulse amplitude that was fully restored by testosterone replacement therapy, providing evidence for the importance of androgen in maintaining the GH secretory profile of the male rat (82).
Estradiol-treated rats (sham and gonadectomized) demonstrate a regular pattern of GH responsiveness to GHRH that is typical of what is observed in female rats (82). Loss of this cyclic responsiveness to GHRH is thought to be mediated through alterations in hypothalamic SRIF secretion. The sexual dimorphism of GH secretion in rats, therefore, appears to be related to the temporal pattern of SRIF secretion with females showing a more continuous pattern of SRIF release compared with a more pulsatile pattern in males. The feminizing effects of short-term exposure to estradiol in both sham-operated and gonadectomized rats identifies estradiol as another important modulator of SRIF tone in the neuroregulation of GH secretion and responsible at least in part for the dimorphic nature of GH secretion in the rat (82).
Previous studies of spontaneous GH secretion in humans demonstrates a lack of gender-specific GH secretion until the peripubertal and pubertal periods (83,84), characterized by enhanced GH secretion in response to the opposing effects of testosterone and 17^-estradiol on SRIF release. Testosterone appears to stimulate SRIF release; whether this is related to the direct effects of testosterone or secondary to central aromatization to estradiol is unclear. Spontaneous GH secretion in women is characterized by more frequent GH secretory bursts when compared with men. Trough GH values are slightly lower in men (7).
One recent study demonstrated significant increases in GH release in adult men, 19-24 yr, following pretreatment with increasing doses of pyridostigmine prior to GHRH administration, while adult women failed to respond in a similar fashion to pyridostigmine (85). Previous studies have shown no differences in the GH response to GHRH during the different phases of the menstrual cycle, suggesting that men have higher SRIF tone associated with low cholinergic control of GH. Women appeared to have higher cholinergic tone associated with diminished SRIF levels and a failure of pydridostigmine to augment GHRH-stimulated GH release. Further, women had more pyridostigmine-related side effects presumably related to presence of enhanced cholinergic tone (85). These observations are likely applicable to adolescents.
Studies of spontaneous GH secretion in normal boys and girls show enhanced GH secretion during the pubertal period, characterized by an increase in GH released per secretory event (amplitude), independent of any changes in pulse frequency, duration or GH half-life (86). The change in the GH secretory profile is most evident at night, with a mean nighttime GH concentration highest at testicular volume 10-15 mL in boys (84). Twenty-four-hour spontaneous GH values in late puberty were triple the values seen in prepubertal subjects, and twice the levels seen in adults. The 24-h secretory rates were inversely correlated with BMI and positively correlated with plasma IGF-1 concentrations (86).
Subjects with gonadotropin-dependent and independent forms of precocious puberty also manifest augmented GH secretion. Treatment of central precocious puberty with gonadotropin-releasing hormone (GnRH) agonist therapy reduces mean nighttime GH secretion after 6 mo of gonadal suppression (87); however more recent studies demonstrate spontaneous nocturnal GH secretion is not altered and suggests that decreases in growth velocity associated with GnRH agonist therapy is related to the direct effects of sex steroids on skeletal growth and not to alterations in GH secretion (88). Women using oral contraceptives have greater mean peak GH response to provocative stimuli when compared with women on no medication (89). Estrogen pretreatment prior to GH provocative studies is frequently used to "prime" prepubertal and peripubertal subjects to improve the likelihood that a normal child will have a normal GH response to a variety of stimuli (20).
No differences in mean 12-h GH concentrations was demonstrated between groups of normal-statured males and growth-retarded males with constitutional delay of growth (90). The constitutional growth delay males were significantly shorter, had a greater bone age delay and diminished growth velocity relative to their normal-statured peers. These constitutional growth delay males had a longer secretory burst half-life relative to their normal statured peers, a feature previously described in girls with Turner syndrome (91). Paradoxically, the constitutional growth delay males had a decreased mass of GH released per burst. The authors theorize a deficiency in the amount of GHRH released per GH secretory event further supported by previous work in prepubertal males with constitutional growth delay (92).
Was this article helpful?