HPG axis

via infundibulum (arcuate nucleus) to adenohypophysis (anterior pituitary gonadotroph cells)

Controls synthesis and secretion of GnRH in GnRH neurons. Upstream of GnRH. Hypothalamic expression - ARC and AVPV (species dependent). Expression regulated by gonadal steroids - Regions express ER, PR.

Expressed on GnRH neurones The Kisspeptin/KISS1R system is a component trigger of puberty. Inactivating mutations of KISS1R and Kisspeptin = failure to undergo spontaneous puberty. Activating KISS1R mutations can lead to precocious puberty.

Hypothalamic explants from mice shown kisspeptin administration stimulates GnRH synthesis and secretion. Kisspeptin neurons send projections to GnRH neurons, and binding to KISS1R expressed on GnRH neurons. A bolus of Kisspeptin correlates with a peak of LH secretion. Sexual dimorphic responses - cyclical differences.

Synthesised and secreted from specialised neurons of hypothalamus- GnRH neurons. Secreted in a pulsatile fashion - pulse generator orchestrated. Stimulates the synthesis and secretion of pituitary gonadotrophin hormones - LH and FSH.

Refer to lec slide made of amino acids Protein, signal peptide, GnRH, GAP

GnRH is secreted in pulses from hypothalamus every 30-120min A GnRH pulse stimulates a pulse of LH and FSH secretion from the pituitary Pulsatile GnRH secretion is vital for stimulation of synthesis and secretion of LH/FSH Slow frequency pulse favours FSHb transcription and FSH release, rapid pulse frequency favours LHb transcription and LH release Continuous release results in cessation of response

GnRH bind to GnRH receptor Signal transduction Gonadotrophin gene expression, synthesis and excretion

Includes LH, FSH and hcG They are glycoprotein hormones, are heterodimeric and secreted in pulsatile fashion they all have a common alpha unit Beta unit separate in LH and FSH giving it different properties

Extra cellular, transmembrane, intracellular

In testis: Sertoli cell metabolism In ovaries: Follicular maturation, granulosa cell oestrogen synthesis

Testis: Stimulation of leydig cell androgen synthesis Ovary: theca cell androgen synthesis, ovulation, progesterone production of corpus luteum This supports germ cell growth, maturation and development to enable it to be suitable for maturation

Progesterone Oestrogens Oestradiol and also oestrone Androgens Androstenedione, testosterone, dihydrotestosterone

Leydig cells LHR expression Androstenedione, DHEA, Testosterone production Sertoli cells FSHR expression Sertoli cell metabolism Testosterone dihydrotestosterone

Corpus luteum LHR (and FSHR) expression Progesterone (and oestrogens) • Theca cells LHR expression Testosterone and Androstenedione • Granulosa cells FSHR expression Oestradiol and Oestrone

Peptide hormones Heterodimers 2 isoforms of inhibin: A and B. Inhibin = gonadal, inhibits FSH secretion via direct negative feedback to anterior pituitary. Males: Inhibin B Females: cyclical dependent