Introduction to RED and the HPG Axis Flashcards
What does HPG axis stand for?
Hypothalamus,, pituitary, gonads axis
What is the role of the hypothalamus?
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.
What is GnRH and which organ produces it?
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.
What is Kallmann syndrome?
Failure of GnRH-secreting neurons to migrate during development, resulting in complete infertility.
When is gonadal activation triggered?
At puberty, gonadal activation is triggered by activation of pulsatile GnRH secretion.
Describe the pulsatile nature of GnRH.
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.
Why is it important that GnRH release is pulsatile?
Continuous GnRH production leads to down regulation of GnRH receptors on gonadotroph cells in the pituitary, resulting in no stimulation of FSH/LH release.
How can we block GnRH’s effects?
It is possible to block GnRH effects using an antagonist or agonist to suppress the HPG axis.
What is the pituitary gland and what does it secrete?
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.
What is the structure of the pituitary gland?
The pituitary has 2 lobes: Anterior Pituitary releases ACTH, TSH, GH, LH, FSH, Prolactin; Posterior Pituitary releases ADH, Oxytocin.
Which anterior pituitary hormones are important in reproduction and which cells produce them?
Gonadotropins (FSH and LH) are produced by gonadotrophs. ACTH is produced by corticotrophs, GH by somatotrophs, and Prolactin by lactotrophs.
What are the key gonadotropins of the HPG axis?
FSH and LH.
How do gonadotropins have their effect?
They are glycoproteins that bind receptors on the cell surface and signal internally via G-protein coupled receptors (GPCR).
What is the third gonadotropin not produced by the anterior pituitary but interacts with the HPG axis?
hCG is the third gonadotropin that interacts with the HPG axis and is important for reproduction.
How do the HPG axis vary between sexes?
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.
What are sex steroids produced in gonads derived from and what are the 3 families?
All derived from cholesterol. The three families are Progestagens, Androgens, and Oestrogens.
Describe the structure of sex steroids.
They are lipid soluble, have nuclear receptors, and act via steroid response elements (SREs). They are bound to carrier proteins.
What are the types of progestagens and their functions?
Types include Progesterone, 17α-hydroxyprogesterone, and 20α-hydroxyprogesterone. Functions include preparation of the uterus for pregnancy and maintenance during pregnancy.
What are the types of androgens and their functions?
Types include DHT, Testosterone, Androstenedione, and DHEA. Functions include development and maintenance of the male reproductive system and regulation of gonadotropins.
What are the types of oestrogens and their functions?
Types include Oestradiol, Oestriol, and Oestrone. Functions include stimulation of endometrial proliferation and regulation of gonadotropins.
How does the predominant oestrogen vary during the female lifecycle?
Oestradiol from puberty to menopause, Oestriol during pregnancy, and Oestrone post-menopause.
What is potency in the context of hormones?
Potency depends on how well a steroid fits the binding site on its receptor. Each hormone has a different potency.
How can steroid action be regulated?
By altering the amount of steroid produced or the amount/structure of the receptor.
Describe the clinical problems of the HPG axis.
Issues with the HPG axis can affect fertility, leading to central/secondary hypogonadism or primary hypogonadism.
Describe hormone levels in central vs primary hypogonadism.
Central: low sex steroids, low LH/FSH. Primary: low sex steroids, high LH/FSH.
How does prolactin play a role in the HPG axis?
Prolactin interacts with the HPG axis and inhibits gonadal activity through central suppression of GnRH.
Why is prolactin a good thing when you just had a baby?
It induces lactation.
What are sex steroids?
Sex steroids are hormones that regulate reproductive functions.
Low LH/FSH indicates low sex steroids, while high LH/FSH indicates primary low sex steroids.
How does prolactin play a role in the HPG axis?
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.
Why is prolactin beneficial after childbirth?
Prolactin induces lactational amenorrhea, acting as a natural contraceptive by suppressing the HPG axis to prevent ovulation.
When can prolactin be problematic during pregnancy?
Hyperprolactinemia can cause fertility issues and galactorrhea if a woman is not postpartum and is trying to conceive.
How does gametogenesis differ in males and females?
In males, gametogenesis is continuous with constant sperm production. In females, it is cyclic, producing one oocyte per month.
What are the three phases of the menstrual cycle?
The menstrual cycle has three phases: Follicular/proliferative phase, Ovulation, and Luteal/secretory phase.
What is the normal duration of the menstrual cycle?
The normal duration of the menstrual cycle is 26-32 days, with the luteal phase lasting 14 days and the follicular phase varying.
When should FSH/LH be tested in the menstrual cycle?
FSH/LH testing is done on day 2 or 3 of the menstrual cycle to assess ovarian reserve.
When should ovulation be tested in the menstrual cycle?
Ovulation testing is done by measuring progesterone (P4) at day 21/28 during the luteal phase; high P4 indicates ovulation.
What is oligomenorrhea?
Oligomenorrhea is defined as having fewer than 9 menstrual cycles in the last 12 months.
What is amenorrhea?
Amenorrhea is the absence of menstrual bleeding for the last 6 months, which can be primary (never bled) or secondary (stopped after regular cycles).
What is menorrhagia?
Menorrhagia refers to heavy menstrual periods.
What is dysmenorrhea?
Dysmenorrhea is characterized by painful menstrual periods.
What is menopause?
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.
How can we clinically exploit the HPG axis?
We can exploit the HPG axis through hormonal contraception, fertility treatments like IVF, and treatment of prostate cancer.
What is hormonal contraception?
Hormonal contraception uses synthetic progestagens and oestrogens to suppress ovulation and thicken cervical mucus, also thinning the endometrium.
How is IVF related to the HPG axis?
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.
How is the HPG axis used in prostate cancer treatment?
GnRH antagonists are used to suppress testosterone production, aiding in the treatment of prostate cancer.
