Published on 22/03/2015 by admin
Filed under Pediatrics
Last modified 22/03/2015
This article have been viewed 1190 times
Chapter 555 Physiology of Puberty
Luigi Garibaldi, Wassim Chemaitilly
Between early childhood and approximately 8-9 yr of age (prepubertal stage), the hypothalamic-pituitary-gonadal axis is dormant, as reflected by undetectable serum concentrations of luteinizing hormone (LH) and sex hormones (estradiol in girls, testosterone in boys). One to 3 yr before the onset of clinically evident puberty, low serum levels of LH during sleep become demonstrable (peripubertal period). This sleep-entrained LH secretion occurs in a pulsatile fashion and reflects endogenous episodic discharge of hypothalamic gonadotropin-releasing hormone (GnRH). Nocturnal pulses of LH continue to increase in amplitude and, to a lesser extent, in frequency as clinical puberty approaches. This pulsatile secretion of gonadotropins is responsible for enlargement and maturation of the gonads and the secretion of sex hormones. The appearance of the secondary sex characteristics in early puberty is the visible culmination of the sustained, active interaction occurring among hypothalamus, pituitary, and gonads in the peripubertal period. By mid-puberty, LH pulses become evident even during the daytime and occur at about 90- to 120-min intervals. A second critical event occurs in middle or late adolescence in girls, in whom cyclicity and ovulation occur. A positive feedback mechanism develops whereby increasing levels of estrogen in midcycle cause a distinct increase of LH.
The increasing secretion of hypothalamic GnRH in a pulsatile fashion thus underlies the onset of pubertal development. The resulting “GnRH pulse generator” is regulated by multiple neurotransmitters, including glutamic acid and kisspeptin (both stimulatory) and γ-aminobutyric acid and pre-proenkephalin (both inhibitory). GnRH secretion is also regulated by factors produced by the glial cells, such as transforming growth factor β (TGF-β). The role of GnRH is fundamental; its pulsed administration can reproduce pubertal development in sexually immature or gonadotropin-deficient animals and humans. Mutations of the GPR54 gene (a G protein–coupled receptor gene whose ligand is kisspeptin) cause an autosomal recessive form of hypogonadotropic hypogonadism. Defects of this receptor-ligand system do not affect GnRH neuronal migration, in contrast to the X-linked hypogonadotropic hypogonadism of Kallmann syndrome; rather they impair the activity of GnRH-secreting neurons in the hypothalamus. Conversely, TGF-β signaling has been associated with the occurrence of central precocious puberty in patients with hypothalamic hamartoma.
Nelson Textbook of Pediatrics Expert Consult
