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1

What is the HPG axis

The hypothalamic–pituitary–gonadal axis
multiple endocrine glands working together as a system

2

What does the HPG axis do?

regulate development, reproduction, and ageing in animals

3

What do endocrine glands do?

secrete hormones into the bloodstream; the hormones travel to and act on other organs or tissues

4

What are the components of the HPG?

• Hypothalamus
• Anterior pituitary
• Testes/ovaries

5

What is the hypothalamus?

Component of forebrain; part of the diencephalon

6

What does the hypothalamus do?

Regulates many core body functions (homeostatic functions) eg. Metabolism, growth, reproduction, stress.

7

How is the hypothalamus in contact with the anterior pituitary gland?

Secretes a peptide hormone: gonadotrophin releasing hormone (GnRH)
Critical component of the reproductive system

8

What are the two parts of the pituitary gland?

• Posterior and anterior (distinct lobes); derived from separate types of cells during embryogenesis; different functions.

9

What is the anterior pituitary gland?

An endocrine gland

10

What is the anterior pituitary gland made up of?

different groups of cells:
o Thyrotropes (Thyroid-stimulating hormone; TSH)
o Somatotropes (Growth hormones)
o Gonadotrophs (Follicle-stimulating hormone; FSH and Luteinising hormone; LH)
o Corticotropes (adrenocorticotropic hormone; ACTH)
o Lactotropes (prolactin; PRL)

11

How does GnRH connect the three systems?

GnRH from the hypothalamus travels in the portal blood to the anterior pituitary where it acts on gonadotrophs

12

How does GnRH positively regulate cells proliferation and hormone production?

through a G-protein-coupled receptor (GnRHr)

13

What does GnRHr signalling stimulate?

Production of FSH and LH

14

What is GnRH?

short polypeptide

15

What do FSH and LH do?

act on different types of cells and these cells ten produce different hormones

16

What are the three main types of sex steroid?

progestagens, androgens and oestrogens

17

What are sex steroids derived from?

a common precursor: cholesterol

18

Interconversion of sex steroids is via?

a biosynthetic network

19

Action of these steroids is dictated by tissue-specific receptors

T

20

Once inside a cell a steroid ...

steroid-receptor complexes bind to steroid response elements on DNA and impact on transcription

21

What affect does oestrogen have on gonadotrophs?

1. Oestrogen binds to the oestrogen receptor (ER) on the gonadotroph
2. The hormone-receptor complex translocates to the nucleus and mediates negative transcriptional control of target genes through oestrogen response elements (EREs)
3. Suppression of transcription
4. This regulates the production of FSH and LH

22

What family are th inhibins and activins from?

TGFβ

23

What do inhibins/activins do on gonadotrophs?

bind to inhibin and activin receptors on the gonadotroph cell
They act to regulate FSH and LH expression

24

What is LH and FSH output predominantly regulated by in females?

secretory products from the ovary

25

In females Negative feedback on LH and FSH is by?

: oestrogens, progestogens and inhibins

26

in females Positive feedback on LH and FSH is by?

activin; oestradiol (an oestrogen)

27

What is the effect of oestradiol in females?

at low concentrations acts to negatively regulate LH expression but at high levels it acts to positively regulate expression

28

What is the effect of progesterone in females?

o High concentration seen in luteal phase of menstrual cycle (after ovulation) enhances the negative feedback of oestradiol
o At certain levels, the positive feedback effect of oestradiol is blocked

29

What level does feedback act on the HPG axis?

both the levels of the pituitary and at the level of the hypothalamus

30

How do the waves affect the hypothalamus?

both the magnitude and frequency of the waves