L01 - The HPG Axis Flashcards by J M

Describe the HPG axis in males.

1 - The hypothalamus secretes GnRH

2 - GnRH stimulates the anterior pituitary to release FSH and LH

3 - FSH and LH stimulate the testes to produce inhibin and testosterone

4 - Inhibin has a negative feedback effect on the anterior pituitary

5 - Testosterone has a negative feedback effect on the anterior pituitary and hypothalamus

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How does the female HPG axis differ from the male HPG axis?

1 - Oestrogen and progesterone produced by the ovaries

2 - Both oestrogen and progesterone have a negative feedback effect on both the anterior pituitary and hypothalamus (whereas inhibin only affects the anterior pituitary)

3 - Oestrogen can also have a positive feedback effect on both the anterior pituitary and hypothalamus

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Where is the hypothalamus located?

Base of the brain between the midbrain and forebrain

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What type of molecule is GnRH?

Peptide hormone

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What is Kallmann syndrome?

Failure of GnRH-secreting neurones to migrate during development, causing infertility

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At puberty, what triggers gonadal activation?

Pulsatile GnRH secretion

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How does the pituitary acquire resistance to the effects of GnRH?

Continuous GnRH secretion leads to downregulation of GnRH receptors on the surface of anterior pituitary gonadotrophs

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Which 6 hormones are secreted by the anterior pituitary?

1 - Adrenocorticotropic hormone

2 - Thyroid-stimulating hormone

3 - Growth hormone

4 - Luteinising hormone

5 - Follicle-stimulating hormone

6 - Prolactin

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Which 2 hormones are secreted by the posterior pituitary?

1 - Antidiuretic hormone

2 - Oxytocin

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Which hormones are secreted by gonadotrophs?

Give an example of another other gonadotropin that is not secreted by gonadotrophs.

1 - Follicle-stimulating hormone.

2 - Luteinising hormone.

Human chorionic gonadotropin (hCG)

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Which cells secrete ACTH?

Corticotrophs

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Which cells secrete GH?

Somatotrophs

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Which cells secrete prolactin?

Lactotrophs

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What type of molecules are FSH & LH?

Glycoproteins

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What type of receptors are targeted by FSH and LH?

GPCRs

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Which cells secrete hCG?

Trophoblast cells

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Which cells are the targets of LH?

1 - Leydig cells (male)

2 - Theca & granulosa cells (female)

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Which cells are the targets of FSH?

1 - Sertoli cells (male)

2 - Granulosa cells (female)

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Which cells are the target of hCG?

Luteal cells of the corpus luteum

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What are the receptors for the gonadotropins?

1 - Luteinizing hormone-choriogonadotropin receptor (LHCGR): LH and hCG

2 - Follicle-stimulating hormone receptor (FSHR): FSH

What are the routes of communication from the hypothalamus to the pituitary?

1 - Direct neural connection

2 - Indirect via the vasculature

What are the 3 main families of sex steroid hormones?

1 - Progestogens (released from gonads and placenta)

2 - Androgens (released from gonads and adrenal glands)

3 - Oestrogens (released from gonads, liver, adrenal glands, adipose tissue and placenta)

From which molecule are sex steroid hormones derived?

Cholesterol (via acetate)

On which domain of which type of receptor do sex steroid hormones act?

Steroid response elements (SREs) of nuclear receptors

List 3 carrier proteins that bind to sex steroid hormones.

1 - Albumin 2 - Sex hormone binding globulin (SHBG) 3 - Androgen binding protein (ABP)

List 3 progestogens.

1 - Progesterone (P4) 2 - 17⍺-hydroxyprogesterone (17⍺-OHP) 3 - 20⍺-hydroxyprogesterone (20⍺-OHP)

List 4 androgens.

1 - 5⍺-dihydrotestosterone (DHT) 2 - Testosterone (T) 3 - Androstenedione (A4) 4 - Dehydroepiandrosterone (DHEA)

List 3 oestrogens. In which stages of life are these hormones particularly active?

1 - Oestradiol 17β (E2) - puberty to menopause 2 - Oestriol (E3) - pregnancy 3 - Oestrone (E1) - post-menopause

List 5 functions of progestogens.

1 - Preparation & maintenance of uterus during pregnancy 2 - Growth of mammary glands 3 - Suppression of lactation 4 - Catabolic effects 5 - Regulation of gonadotropins

List 5 functions of androgens.

1 - Development & maintenance of male reproductive system 2 - Secondary sexual characteristics 3 - Sexual function 4 - Support spermatogenesis 5 - Regulation of gonadotropins

List 4 functions of oestrogens.

1 - Secondary sexual characteristics 2 - Stimulate growth & activity of mammary glands 3 - Stimulate proliferation of endometrium for progesterone action 4 - Regulate gonadotropins

Give an example of a sex steroid hormone that binds to receptors of classes other than their own.

Synthetic progestogens in the contraceptive pill can be androgenic and cause side effects such as acne

Give an example of a sex steroid hormone receptor antagonist.

Mifepristone is an anti-progestogen

How do sex steroids interact with gonadotropins?

Sex steroids are both regulated by & regulate gonadotropins of the anterior pituitary via feedback loops

Which component of the HPG axis is dysfunctional with central hypogonadism?

Hypothalamus/pituitary

Which component of the HPG axis is dysfunctional with primary hypogonadism?

Ovary/testis

Which sex is more likely to experience endocrine causes of infertility?

Females

When do levels of prolactin increase?

During pregnancy & breastfeeding

What is the function of prolactin?

Inhibits gonadal activity through the central suppression of GnRH, which decreases FSH/LH, and induces lactational amenorrhoea

How does gametogenesis in males differ from gametogenesis in females?

- Males: gametogenesis is continuous i.e. there is constant sperm production - Females: gametogenesis is cyclic i.e. there is one oocyte produced per month

What are the 3 phases of the menstrual cycle?

1 - Follicular/proliferative 2 - Ovulation 3 - Luteal/secretory

What is the average duration of the menstrual cycle?

26-32 days (average 28 days)

How long is the luteal phase of the menstrual cycle?

14 days

Which phase of the menstrual cycle is variable in length?

Follicular phase

By convention, when are FSH and LH measured clinically?

Day 2/3

# Define ovarian reserve. How can ovarian reserve be measured?

- Ovarian reserve is a term that is used to determine the capacity of the ovary to provide egg cells that are capable of fertilisation - It can be measured by measuring FSH & LH on day 2/3

Define oligomenorrhoea.

<9 cycles in the last 12 months

Define amenorrhoea.

No bleed in the last 6 months. Either primary (never) or secondary (ceased)

What hormonal changes accompany menopause?

- No production of progesterone or oestrogen by the ovaries | - Loss of negative feedback by sex steroids leads to high FSH/LH levels