Neuroendocrine mechanisms mediating awakening of the human gonadotropic axis in puberty

Abstract

The hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator presides over the pulsatile and feedback-regulated activities of the pituitary-gonadal axis. Awakening of synchronous activity of the GnRH neuronal ensemble in the earliest stages of puberty heralds the onset of full activation of the reproductive axis in girls and boys. Progression from prepuberty to adulthood in boys is directed by marked (30-fold) amplitude enhancement of pulsatile luteinizing hormone (LH) secretion, as assessed by an ultrasensitive immunofluorometric assay and deconvolution analysis. There is a much less apparent rise in LH secretory burst frequency (approximately 1.3-fold increase). Consequently, human puberty is an amplitude-driven neuroendocrine maturational process. However, less is known about pulsatile follicle-stimulating hormone (FSH) release in puberty. Multiple pathophysiologies that result in hypogonadotropic hypogonadism can converge on a final common mechanism of attenuated hypothalamic GnRH pulse generator output and hence reduced LH (and FSH) secretion. Disturbances may take the form of reduced GnRH pulse frequency and/or attenuated GnRH secretory burst mass. When the pathophysiology of hypogonadism originates exclusively in a failed GnRH pulse generator, then either treatment of the primary disease process where possible (e.g., by refeeding in starvation, improved metabolic control in diabetes mellitus, dopamine agonist treatment in hyperprolactinemia, etc) and/or treatment with pulsatile GnRH (e.g., in Kallmann's syndrome, isolated hypothalamic lesions, etc.) can provide relevant therapeutic options in children and adults.

Risk of Cancer in Children, Adolescents, and Young Adults with Autistic Disorder

“…Puberty starts between ages 9-14 years with pulsatile release of luteinizing hormone and the follicle-stimulating hormone, which stimulate gonadal maturation and production of sex steroids, most notably testosterone in boys and estradiol in girls. 22 Most malignant tumors of the ovary and testis in pediatric patients are of germ cell origin, and sex steroids are assumed to be important for the rise and progression of germ cell cancer. 23 Even intrauterine hormonal exposure (ie, synthetic estrogen diethylstilbestrol) has been linked to risk of testicular cancer.…”

Sex differences in the renal transforming growth factor-β1 system after puberty

“…Many alterations in neuroendocrine physiology occur during this period of growth. Any or all of these may influence the activity of TGF-β in the kidney [42,43]. For example, growth hormone has been shown to increase angiotensin II binding and signalling in rat mesangial cells [44].…”

Puberty permits increased expression of renal transforming growth factor-?1 in experimental diabetes

“…These phenomena are under the control of the hypothalamic-pituitary axis [24,25]. There are a variety of potential modulators of renal growth and TGF-β activity during puberty, including gonadotropins, activins, inhibins, growth hormone, insulin-like growth factor-I, leptin, and other hormones.…”