Flashcards in Hypothalamic - Pituitary Gonadal Axis I Deck (54)
What are the 7 things needed to reproduce?
→Correct process of sex determination (genotypic sex) and differentiation (phenotypic sex)
→Sexual maturation- Puberty
→Production and storage of sufficient supply of gametes
→Correct number of chromosomes in egg and sperm
→Actual sexual intercourse
→Fertilisation, implantation, embryonic and placental development
→ nurture individual until capable of “independent” life
What is an example of positive feedback?
Describe how the HPG axis works?
→+ve drive from the hypothalamus which activates the pituitary
→ +ve drive causing hormonal release from the pituitary
→ Causes release of steroid hormones from the gonads
→ Work in a -ve feedback to regulate their production
What does type of hormones does the hypothalamus produce?
→ Peptide hormones
What hormones does the hypothalamus produce?
→Gonadotropin releasing hormone
What hormones does the pituitary produce?
→ Follicle stimulating hormone
What hormones do the gonads produce?
Describe the HPG axis in relation to FSH and LH?
→ GnRH is released from the hypothalamus
→ This binds to the receptor on the anterior pituitary
→ LH and FSH are secreted
→ FSH and LH are released into the circulation and bind to their receptors on the gonads
→ this co-ordinates the secretion of estrogen, progesterone and androgens
Where is GnRH secreted into?
→ Into the primary plexus of the median eminence
Where does GnRH travel after it is secreted?
→ Into the hypophyseal portal into the anterior pituitary
What does GnRH act on?
→ The gonadotroph cells in the anterior pituitary
What is the function of kisspeptin?
→ Master controller of puberty
Where is kisspeptin expressed?
→ In the arcuate nucleus
→ AVPV nucleus
What do kisspeptin neurons do?
→ They send signals upstream of GnRH to neurons
What receptor do the kisspeptin neurons bind to?
→ GPR54 receptor on GnRH neurons
What can kisspeptin 54 cross?
→ blood brain barrier
What type of hormone is kisspeptin?
→ Peptide hormone that is cleaved from a large pre-pro structure
What is GnRH secreted in response to and where?
→ Synthesized and secreted in response to kisspeptin
→ From GnRH neurons
What type of release is GnRH?
Where does GnRH bind?
→ To the GnRH receptor on gonadotroph cells of the anterior pituitary
Where does GnRH travel from and to?
→ from the arcuate nucleus to the median eminence to the anterior pituitary
What is GnRH produced from?
→ a Prepro protein
What is GnRH spliced into?
What is GnRh co-secreted with?
When is GnRh secreted?
→ every 30-120 minutes
What does GnRH stimulate?
→ A pulse of LH and FSH secretion from the pituitary
What types of GnRH pulse favor LH and what types favor FSH?
→ slow frequency - FSH
→ rapid frequency - LH
What does continuous release of GnRH lead to?
→ Cessation of response
What hormone gets produced after a surge in LH and estradiol and what happens to the follicle?
→ Remodelling of the ovarian follicle into the corpus luteum
How does native GnRh binding work?
→ GnRH binds to its receptor
→ It activates a signaling pathway cascade
→ Stimulates gonadotrophin synthesis and secretion
→ GnRH dissociates from its receptor
→ Receptor is ready to respond to the next GnRH pulse
How does a GnRH agonist work?
→ Binds to the receptor
→ Activates signaling
→ Stimulates gonadotrophin synthesis and secretion at first
→ Doesn't dissociate
→ GnRH is uncoupled
→ Receptor is unresponsive
How does a GnRH antagonist work?
→ Binds to the receptor
→ Blocks the receptor
→ No downstream effect and LH and FSH are switched off
What are 6 uses of GnRH analogues?
→ Prostate cancer
→ Breast , ovarian and endometrial cancer
How does GnRH cause FSH and LH to increase?
→ Increases the transcription and translation of the subunits that make up LH and FSH
What are the gonadotrophin hormones?
What type of peptides are the gonadotrophin hormones?
→ Heterodimeric peptides
→ Common a subunit
→ Hormone specific B subunit
What is required for biological function of heterodimeric peptides?
→ N linked carbohydrate side chains
What happens if N linked carbohydrate chains are deglycosylated?
→ They still bind but they are inhibitory
Which subunit of the gonadotrophic hormones are made in excess?
→A subunits are synthesized in excess
What is the function of LH in the testes?
→ Stimulation of Leydig cells and androgen synthesis
What is the function of LH in the ovary?
→ Stimulation of Theca cells and androgen synthesis
→ Progesterone production of corpus luteum
What is the function of FSH in the testis?
→ Regulation of Sertoli cell metabolism
What is the function of FSH in the ovary?
→ Follicular maturation
→ Granulosa cell - estrogen synthesis
Where are the Leydig cells between?
→ Seminiferous tubules
What do Leydig cells express?
→ LH receptor
What is lining the seminiferous tubules and what is their function?
→ Sertoli cells which express the FSH receptor
→ Co-ordinate spermatogenesis
What are the cells that line the ovarian follicle called?
→ Theca cells
What do Theca cells do?
→ Stimulate androgen production
What do granulosa cells express?
→ FSH receptors
How are androgens converted to estrogens?
→ Androgens cross the basement membrane and go to the granulosa cells
→ They are converted via the aromatase enzyme.
What regulates aromatase?
→ FSH receptors
What is produced in the corpus luteum?
Describe the HPG axis in females?
→ Kisspeptin and GnRH are released from the hypothalamus
→ GnRH travels to the gonadotroph cells of the anterior pituitary
→ It causes the synthesis and secretion of LH and FSH
→ LH binds to its receptor on Theca cells
→ Stimulates androgen production
→ FSH binds to its receptor on Granulosa cells
→ This causes the conversion of androgens to estrogens
→ Within the luteal phase you get progesterone produced
→ These feedback negatively except estradiol