Introduction to RED and the HPG Axis

Question 1

What does HPG axis stand for?

Answer 1

Hypothalamus,, pituitary, gonads axis

Question 2

What is the role of the hypothalamus?

Answer 2

Found at the base of the brain, between the midbrain and forebrain. It is a collection of brain nuclei or centres that controls endocrine function via the pituitary gland.

Question 3

What is GnRH and which organ produces it?

Answer 3

Gonadotropin releasing hormone (GnRH) is a peptide hormone produced by the hypothalamus. In its active form, it’s a decapeptide derived from a 92 aa prepropeptide.

Question 4

What is Kallmann syndrome?

Answer 4

Failure of GnRH-secreting neurons to migrate during development, resulting in complete infertility.

Question 5

When is gonadal activation triggered?

Answer 5

At puberty, gonadal activation is triggered by activation of pulsatile GnRH secretion.

Question 6

Describe the pulsatile nature of GnRH.

Answer 6

In males, frequency of pulses is fairly constant. In females, frequency varies during the menstrual cycle: low frequency during luteal phase, medium frequency favours secretion of FSH, and high frequency favours secretion of LH.

Question 7

Why is it important that GnRH release is pulsatile?

Answer 7

Continuous GnRH production leads to down regulation of GnRH receptors on gonadotroph cells in the pituitary, resulting in no stimulation of FSH/LH release.

Question 8

How can we block GnRH’s effects?

Answer 8

It is possible to block GnRH effects using an antagonist or agonist to suppress the HPG axis.

Question 9

What is the pituitary gland and what does it secrete?

Answer 9

A pea-sized gland at the base of the brain that secretes a range of hormones regulated by signals from the hypothalamus and feedback loops involving circulating hormones.

Question 10

What is the structure of the pituitary gland?

Answer 10

The pituitary has 2 lobes: Anterior Pituitary releases ACTH, TSH, GH, LH, FSH, Prolactin; Posterior Pituitary releases ADH, Oxytocin.

Question 11

Which anterior pituitary hormones are important in reproduction and which cells produce them?

Answer 11

Gonadotropins (FSH and LH) are produced by gonadotrophs. ACTH is produced by corticotrophs, GH by somatotrophs, and Prolactin by lactotrophs.

Question 12

What are the key gonadotropins of the HPG axis?

Answer 12

FSH and LH.

Question 13

How do gonadotropins have their effect?

Answer 13

They are glycoproteins that bind receptors on the cell surface and signal internally via G-protein coupled receptors (GPCR).

Question 14

What is the third gonadotropin not produced by the anterior pituitary but interacts with the HPG axis?

Answer 14

hCG is the third gonadotropin that interacts with the HPG axis and is important for reproduction.

Question 15

How do the HPG axis vary between sexes?

Answer 15

The HP part of the axis is essentially the same for both sexes, but the G part is different: female gonads are ovaries and male gonads are testes.

Question 16

What are sex steroids produced in gonads derived from and what are the 3 families?

Answer 16

All derived from cholesterol. The three families are Progestagens, Androgens, and Oestrogens.

Question 17

Describe the structure of sex steroids.

Answer 17

They are lipid soluble, have nuclear receptors, and act via steroid response elements (SREs). They are bound to carrier proteins.

Question 18

What are the types of progestagens and their functions?

Answer 18

Types include Progesterone, 17α-hydroxyprogesterone, and 20α-hydroxyprogesterone. Functions include preparation of the uterus for pregnancy and maintenance during pregnancy.

Question 19

What are the types of androgens and their functions?

Answer 19

Types include DHT, Testosterone, Androstenedione, and DHEA. Functions include development and maintenance of the male reproductive system and regulation of gonadotropins.

Question 20

What are the types of oestrogens and their functions?

Answer 20

Types include Oestradiol, Oestriol, and Oestrone. Functions include stimulation of endometrial proliferation and regulation of gonadotropins.

Question 21

How does the predominant oestrogen vary during the female lifecycle?

Answer 21

Oestradiol from puberty to menopause, Oestriol during pregnancy, and Oestrone post-menopause.

Question 22

What is potency in the context of hormones?

Answer 22

Potency depends on how well a steroid fits the binding site on its receptor. Each hormone has a different potency.

Question 23

How can steroid action be regulated?

Answer 23

By altering the amount of steroid produced or the amount/structure of the receptor.

Question 24

Describe the clinical problems of the HPG axis.

Answer 24

Issues with the HPG axis can affect fertility, leading to central/secondary hypogonadism or primary hypogonadism.

Question 25

Describe hormone levels in central vs primary hypogonadism.

Answer 25

Central: low sex steroids, low LH/FSH. Primary: low sex steroids, high LH/FSH.

Question 26

How does prolactin play a role in the HPG axis?

Answer 26

Prolactin interacts with the HPG axis and inhibits gonadal activity through central suppression of GnRH.

Question 27

Why is prolactin a good thing when you just had a baby?

Answer 27

It induces lactation.

Question 28

What are sex steroids?

Answer 28

Sex steroids are hormones that regulate reproductive functions. ## Footnote Low LH/FSH indicates low sex steroids, while high LH/FSH indicates primary low sex steroids.

Question 29

How does prolactin play a role in the HPG axis?

Answer 29

Prolactin interacts with the HPG axis, increasing dramatically during pregnancy and breastfeeding, inhibiting gonadal activity through central suppression of GnRH, leading to decreased LH/FSH.

Question 30

Why is prolactin beneficial after childbirth?

Answer 30

Prolactin induces lactational amenorrhea, acting as a natural contraceptive by suppressing the HPG axis to prevent ovulation.

Question 31

When can prolactin be problematic during pregnancy?

Answer 31

Hyperprolactinemia can cause fertility issues and galactorrhea if a woman is not postpartum and is trying to conceive.

Question 32

How does gametogenesis differ in males and females?

Answer 32

In males, gametogenesis is continuous with constant sperm production. In females, it is cyclic, producing one oocyte per month.

Question 33

What are the three phases of the menstrual cycle?

Answer 33

The menstrual cycle has three phases: Follicular/proliferative phase, Ovulation, and Luteal/secretory phase.

Question 34

What is the normal duration of the menstrual cycle?

Answer 34

The normal duration of the menstrual cycle is 26-32 days, with the luteal phase lasting 14 days and the follicular phase varying.

Question 35

When should FSH/LH be tested in the menstrual cycle?

Answer 35

FSH/LH testing is done on day 2 or 3 of the menstrual cycle to assess ovarian reserve.

Question 36

When should ovulation be tested in the menstrual cycle?

Answer 36

Ovulation testing is done by measuring progesterone (P4) at day 21/28 during the luteal phase; high P4 indicates ovulation.

Question 37

What is oligomenorrhea?

Answer 37

Oligomenorrhea is defined as having fewer than 9 menstrual cycles in the last 12 months.

Question 38

What is amenorrhea?

Answer 38

Amenorrhea is the absence of menstrual bleeding for the last 6 months, which can be primary (never bled) or secondary (stopped after regular cycles).

Question 39

What is menorrhagia?

Answer 39

Menorrhagia refers to heavy menstrual periods.

Question 40

What is dysmenorrhea?

Answer 40

Dysmenorrhea is characterized by painful menstrual periods.

Question 41

What is menopause?

Answer 41

Menopause occurs around age 50 when ovarian reserve is depleted, leading to cessation of ovulation and production of sex steroids, resulting in high FSH/LH levels.

Question 42

How can we clinically exploit the HPG axis?

Answer 42

We can exploit the HPG axis through hormonal contraception, fertility treatments like IVF, and treatment of prostate cancer.

Question 43

What is hormonal contraception?

Answer 43

Hormonal contraception uses synthetic progestagens and oestrogens to suppress ovulation and thicken cervical mucus, also thinning the endometrium.

Question 44

How is IVF related to the HPG axis?

Answer 44

In IVF, the HPG axis is down-regulated with GnRH agonists/antagonists, followed by stimulation of follicle development with FSH and inducing oocyte maturation with hCG.

Question 45

How is the HPG axis used in prostate cancer treatment?

Answer 45

GnRH antagonists are used to suppress testosterone production, aiding in the treatment of prostate cancer.