1
Q

What are the 7 things needed to reproduce?

A

β†’Correct process of sex determination (genotypic sex) and differentiation (phenotypic sex)
β†’Sexual maturation- Puberty
β†’Production and storage of sufficient supply of gametes
β†’Correct number of chromosomes in egg and sperm
β†’Actual sexual intercourse
β†’Fertilisation, implantation, embryonic and placental development
β†’ nurture individual until capable of β€œindependent” life

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2
Q

What is an example of positive feedback?

A

β†’ Ovulation

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3
Q

Describe how the HPG axis works?

A

β†’+ve drive from the hypothalamus which activates the pituitary
β†’ +ve drive causing hormonal release from the pituitary
β†’ Causes release of steroid hormones from the gonads
β†’ Work in a -ve feedback to regulate their production

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4
Q

What does type of hormones does the hypothalamus produce?

A

β†’ Peptide hormones

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5
Q

What hormones does the hypothalamus produce?

A

β†’Gonadotropin releasing hormone

β†’kisspeptin

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6
Q

What hormones does the pituitary produce?

A

β†’ Follicle stimulating hormone

β†’ LH

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7
Q

What hormones do the gonads produce?

A
β†’ Estradiol
β†’ Progesterone
β†’ Testosterone
β†’ Inhibin
β†’ Activin
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8
Q

Describe the HPG axis in relation to FSH and LH?

A

β†’ GnRH is released from the hypothalamus
β†’ This binds to the receptor on the anterior pituitary
β†’ LH and FSH are secreted
β†’ FSH and LH are released into the circulation and bind to their receptors on the gonads
β†’ this co-ordinates the secretion of estrogen, progesterone and androgens

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9
Q

Where is GnRH secreted into?

A

β†’ Into the primary plexus of the median eminence

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10
Q

Where does GnRH travel after it is secreted?

A

β†’ Into the hypophyseal portal into the anterior pituitary

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11
Q

What does GnRH act on?

A

β†’ The gonadotroph cells in the anterior pituitary

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12
Q

What is the function of kisspeptin?

A

β†’ Master controller of puberty

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13
Q

Where is kisspeptin expressed?

A

β†’ In the arcuate nucleus

β†’ AVPV nucleus

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14
Q

What do kisspeptin neurons do?

A

β†’ They send signals upstream of GnRH to neurons

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15
Q

What receptor do the kisspeptin neurons bind to?

A

β†’ GPR54 receptor on GnRH neurons

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16
Q

What can kisspeptin 54 cross?

A

β†’ blood brain barrier

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17
Q

What type of hormone is kisspeptin?

A

β†’ Peptide hormone that is cleaved from a large pre-pro structure

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18
Q

What is GnRH secreted in response to and where?

A

β†’ Synthesized and secreted in response to kisspeptin

β†’ From GnRH neurons

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19
Q

What type of release is GnRH?

A

β†’ Pusatile

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20
Q

Where does GnRH bind?

A

β†’ To the GnRH receptor on gonadotroph cells of the anterior pituitary

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21
Q

Where does GnRH travel from and to?

A

β†’ from the arcuate nucleus to the median eminence to the anterior pituitary

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22
Q

What is GnRH produced from?

A

β†’ a Prepro protein

23
Q

What is GnRH spliced into?

A

β†’ Decapeptide

24
Q

What is GnRh co-secreted with?

A

β†’ GAP

β†’ GnRH

25
Q

When is GnRh secreted?

A

β†’ every 30-120 minutes

26
Q

What does GnRH stimulate?

A

β†’ A pulse of LH and FSH secretion from the pituitary

27
Q

What types of GnRH pulse favor LH and what types favor FSH?

A

β†’ slow frequency - FSH

β†’ rapid frequency - LH

28
Q

What does continuous release of GnRH lead to?

A

β†’ Cessation of response

29
Q

What hormone gets produced after a surge in LH and estradiol and what happens to the follicle?

A

β†’ Progesterone

β†’ Remodelling of the ovarian follicle into the corpus luteum

30
Q

How does native GnRh binding work?

A

β†’ GnRH binds to its receptor
β†’ It activates a signaling pathway cascade
β†’ Stimulates gonadotrophin synthesis and secretion
β†’ GnRH dissociates from its receptor
β†’ Receptor is ready to respond to the next GnRH pulse

31
Q

How does a GnRH agonist work?

A
β†’ Binds to the receptor
β†’ Activates signaling
β†’ Stimulates gonadotrophin synthesis and secretion at first
β†’ Doesn't dissociate
β†’ GnRH is uncoupled
β†’ Receptor is unresponsive
32
Q

How does a GnRH antagonist work?

A

β†’ Binds to the receptor
β†’ Blocks the receptor
β†’ No downstream effect and LH and FSH are switched off

33
Q

What are 6 uses of GnRH analogues?

A
β†’ IVF
β†’ Prostate cancer
β†’ Breast , ovarian and endometrial cancer
β†’ Endometriosis 
β†’ PCOS
β†’ Fibroids
34
Q

How does GnRH cause FSH and LH to increase?

A

β†’ Increases the transcription and translation of the subunits that make up LH and FSH

35
Q

What are the gonadotrophin hormones?

A

β†’ LH
β†’ FSH
β†’hCG

36
Q

What type of peptides are the gonadotrophin hormones?

A

β†’ Heterodimeric peptides
β†’ Common a subunit
β†’ Hormone specific B subunit

37
Q

What is required for biological function of heterodimeric peptides?

A

β†’ N linked carbohydrate side chains

38
Q

What happens if N linked carbohydrate chains are deglycosylated?

A

β†’ They still bind but they are inhibitory

39
Q

Which subunit of the gonadotrophic hormones are made in excess?

A

β†’A subunits are synthesized in excess

40
Q

What is the function of LH in the testes?

A

β†’ Stimulation of Leydig cells and androgen synthesis

41
Q

What is the function of LH in the ovary?

A

β†’ Stimulation of Theca cells and androgen synthesis
β†’ Ovulation
β†’ Progesterone production of corpus luteum

42
Q

What is the function of FSH in the testis?

A

β†’ Regulation of Sertoli cell metabolism

43
Q

What is the function of FSH in the ovary?

A

β†’ Follicular maturation

β†’ Granulosa cell - estrogen synthesis

44
Q

Where are the Leydig cells between?

A

β†’ Seminiferous tubules

45
Q

What do Leydig cells express?

A

β†’ LH receptor

46
Q

What is lining the seminiferous tubules and what is their function?

A

β†’ Sertoli cells which express the FSH receptor

β†’ Co-ordinate spermatogenesis

47
Q

What are the cells that line the ovarian follicle called?

A

β†’ Theca cells

48
Q

What do Theca cells do?

A

β†’ Stimulate androgen production

49
Q

What do granulosa cells express?

A

β†’ FSH receptors

50
Q

How are androgens converted to estrogens?

A

β†’ Androgens cross the basement membrane and go to the granulosa cells
β†’ They are converted via the aromatase enzyme.

51
Q

What regulates aromatase?

A

β†’ FSH receptors

52
Q

What is produced in the corpus luteum?

A

β†’ Progesterone

53
Q

Describe the HPG axis in females?

A

β†’ Kisspeptin and GnRH are released from the hypothalamus
β†’ GnRH travels to the gonadotroph cells of the anterior pituitary
β†’ It causes the synthesis and secretion of LH and FSH
β†’ LH binds to its receptor on Theca cells
β†’ Stimulates androgen production
β†’ FSH binds to its receptor on Granulosa cells
β†’ This causes the conversion of androgens to estrogens
β†’ Within the luteal phase you get progesterone produced
β†’ These feedback negatively except estradiol

54
Q

Describe the HPG axis in males?

A

β†’ From the hypothalamus kisspeptin and GnRH are released
β†’ GnRH travels to the gonadotroph cells of the anterior pituitary
β†’ it causes the synthesis and secretion of LH and FSH
β†’ LH binds to its receptor on Leydig cells to produce testosterone
β†’ FSH binds to its receptor on Sertoli cells to maintain spermatogenesis
β†’ They all feedback negatively