Lecture 12 Puberty and kisspeptin (I) Flashcards
adolescence v puberty
“Adolescence is the phase of gradual transition between childhood and adulthood”
involves brain development and physical changes.
risky behaviour
puberty - physical sexual changes to become fertile.
Secondary sex characteristics appear, physical growth, reproductive competence is achieved.
brain development during adolescence
subcortical regions - amygdala + NAc develop much faster than frontal areas (PFC)
imbalance can lead to risky or emotional behaviour
role of the amygdala?
emotional processing
adolescence response to social or monetary stimuli?
facial expressions increased amygdala response compared to NAc response for monetary reward.
HPG axis?
Hypothalamic-Pituitary-Gonadal (HPG) Axis
GnRH causes LH/FSH release.
LH/FSH activated production of sex steroids, feedback onto hypothalamus/anterior pituitary gland loop.
The hypothalamus is located in the brain and secretes GnRH.[1] GnRH travels down the anterior portion of the pituitary via the hypophyseal portal system and binds to receptors on the secretory cells of the adenohypophysis.[2] In response to GnRH stimulation these cells produce LH and FSH, which travel into the blood stream.[3]
These two hormones play an important role in communicating to the gonads. In females FSH and LH act primarily to activate the ovaries to produce estrogen and inhibin and to regulate the menstrual cycle and ovarian cycle.Estrogen forms a negative feedback loop by inhibiting the production of GnRH in the hypothalamus.
Inhibin acts to inhibit activin, which is a peripherally produced hormone that positively stimulates GnRH-producing cells. Follistatin, which is also produced in all body tissue, inhibits activin and gives the rest of the body more control over the axis. In males LH stimulates the interstitial cells located in the testes to produce testosterone, and FSH plays a role in spermatogenesis. Only small amounts of estrogen are secreted in males. Recent research has shown that a neurosteroid axis exists, which helps the cortex to regulate the hypothalamus’s production of GnRH.[4]
In addition, leptin and insulin have stimulatory effects and ghrelin has inhibitory effects on gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus.[5] Kisspeptin also influences GnRH secretion.[6]
when does onset of puberty occur in females?
when sufficient nutrients attained.
obesity advances onset.
undernutrition delays onset.
physical excercise delays. onset.
Menstruation?
FSH stimulates egg maturation and oestrogen release
oestrogen peaks day 14 just before ovulation, stops FSH production as only 1 egg needed and stimulates LH release.
Day 14 peak LH ovulation day, LH causes mature egg release to uterus which can now be fertilised.
Uterus lining thickens, maintained by Progesterone.
progesterone decreases when no pregnancy occurs, lining sheds and menstruation day 28.
HPG axis in pregnart/non pregenant
oestrogen feeds back onto hypothalamus/anterior pit and progesterone inhibits hypo/anterior pit.
if pregnanart progesterone is taken up by the foetus, increase in progesterone in pregnancy, HPG inhibited throughout and no menstruation.
One of the most important functions of the HPG axis is to regulate reproduction by controlling the uterine and ovarian cycles.[7] In females, the positive feedback loop between estrogen and luteinizing hormone help to prepare the follicle in the ovary and the uterus for ovulation and implantation. When the egg is released, the empty follicle sac begins to produce progesterone to inhibit the hypothalamus and the anterior pituitary thus stopping the estrogen-LH positive feedback loop.
If conception occurs, the placenta will take over the secretion of progesterone; therefore the mother cannot ovulate again. If conception does not occur, decreasing excretion of progesterone will allow the hypothalamus to restart secretion of GnRH. These hormone levels also control the uterine (menstrual) cycle causing the proliferation phase in preparation for ovulation, the secretory phase after ovulation, and menstruation when conception does not occur. The activation of the HPG axis in both males and females during puberty also causes individuals to acquire secondary sex characteristics.
HPG axis in males?
same as female but testis prod testosterone.
testost:
promotes spermatogenesis.
inhibits GnRH and LH/FSH production.
males fertile for life potentially.
In males, the production of GnRH, LH, and FSH are similar, but the effects of these hormones are different.[8] FSH stimulates sustentacular cells to release androgen-binding protein, which promotes testosterone binding. LH binds to the interstitial cells, causing them to secrete testosterone. Testosterone is required for normal spermatogenesis and inhibits the hypothalamus. Inhibin is produced by the spermatogenic cells, which, also through inactivating activin, inhibits the hypothalamus. After puberty these hormones levels remain relatively constant.
males change with age?
less testosterone.
decrease muscle mass increase fat lose libido impotence decreased attention
kisspeptin
Kiss1 gene.
binds GPCR54
GPCR54 renamed Kiss1R
essential for pubertal development and reproductive function
GPCR54 mutations
GPR54 mutations/deletions lead to sexual immaturity, failure of gonadal function and hypogonadotropism
infertile and less sexual hormones
kisspeptin structure?
In primates, the Kiss1 gene encodes a 54 amino acid peptide (kp-54)
In rodents, the mature kisspeptin product is 52 amino acids.
precursor prepro kisspeptin 125 AA long.
numerous kisspeptins of various length.
where is kisspeptin found?
Brain: - AVPV/PeN (anteroventral periventricular nucleus-periventricular nucleus continuum)
- ARC (arcuate nucleus)
Peripheral tissues: placenta, ovary, testis, pituitary, pancreas and adipose tissue
where is the Kiss1R gene found?
Brain: hypothalamus, preoptic area, hippocampus, habenula, amygdala
Peripheral tissues: placenta, testis, pituitary, pancreas and kidney
