Hypothalamic-pituitary-ovarian axis and puberty

Puberty is marked by an increase in the pulsatile secretion of GnRH from the hypothalamus. GnRH secretion is driven by kisspeptin from KNDy neurons of the hypothalamus^[1]. Kisspeptin release is possibly triggered or facilitated by NKB signaling^Δ. GnRH in turn stimulates the secretion of FSH and LH from the gonadotroph cells in the anterior pituitary gland. In girls, FSH stimulates the growth of ovarian follicles and, in conjunction with LH, stimulates production of estradiol by the ovaries. Early in puberty, estradiol stimulates breast development and growth of the skeleton, leading to pubertal growth acceleration. Later in puberty, the interplay between pituitary secretion of FSH and LH and secretion of estradiol by ovarian follicles leads to ovulation and menstrual cycles. The skeletal maturation induced by estradiol eventually results in fusion of the growth plates and cessation of growth.

GnRH: gonadotropin-releasing hormone; KNDy: kisspeptin-neurokinin B-dynorphin; MKRN3: makorin RING-finger protein 3; NKB: neurokinin B; FSH: follicle-stimulating hormone; LH: luteinizing hormone.

* At high concentrations, estradiol has a positive effect on the pituitary, which results in a positive feedback loop between LH and estradiol that eventually leads to the LH surge and ovulation.

¶ The site of action of MKRN3 within the hypothalamus is unknown. One possibility is that MKRN3 may work within KNDy neurons to inhibit puberty initiation by suppressing transcription of the genes that encode kisspeptin and NKB^[2].

Δ It is uncertain whether NKB acts on the KNDy neurons, GnRH neurons, or both and whether these are the primary sites of action. NKB appears to be important for pubertal timing but does not appear to be an obligate part of the hypothalamic-pituitary-gonadal axis, as there can be reproductive endocrine activity in the absence of NKB^[3].

References:

Hughes IA. Releasing the brake on puberty. N Engl J Med 2013; 368:2513.
Abreu AP, Toro CA, Song YB, et al. MKRN3 inhibits the reproductive axis through actions in kisspeptin-expressing neurons. J Clin Invest 2020; 130:4486.
Gianetti E, Tusset C, Noel SD, et al. TAC3/TACR3 mutations reveal preferential activation of gonadotropin-releasing hormone release by neurokinin B in neonatal life followed by reversal in adulthood. J Clin Endocrinol Metab 2010; 95:2857.

Graphic 98701 Version 4.0

خرید پکیج

Hypothalamic-pituitary-ovarian axis and puberty