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499354
L01 - The HPG Axis
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RED Mind Map on L01 - The HPG Axis, created by chris.brees on 22/01/2014.
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Resource summary
L01 - The HPG Axis
Hypothalamus
Found at the base of the brain, between the midbrain and forebrain
Collection of brain nuclei/centres
Controls endocrine function via pituitary gland
Gonadotrophin releasing hormone (GnRH)
Short-life peptide
Pulsatile GnRH secretion at puberty triggers gonad activation
Continuous secretion leads to down regulation of GnRH receptors on gonadotroph cells
Causes lack of LH/FSH release
Can block GnRH effects using antagonist or agonist (due to resulting downregulation of receptors)
Pituitary Gland
Pea-sized gland at the base of the brain
Hormone secretion regulated by thalamus and by feedback loops from circulating hormones
Anterior pituitary hormones in reproduction
Gonadotrophins
FSH
Secreted by gonadotroph cells (ant. pit.)
Acts on sertoli (testes) and granulosa (ovary) cells
Has an alpha chain, a beta chain and two carbohydrate chains
Receptor LHCGR
LH
Secreted by gonadotroph cells (ant. pit.)
Acts on leydig, theca and granulosa cells
Has an alpha chain, a beta chain and a carbohydrate chain
Receptor LHCGR
hCG
Human corionic gonadotrophin
Secreted by trophoblast cells
Acts of luteal cells in the corpus luteum
Has an alpha chain, a beta chain and two carbohydrate chains
FSHR
Bind to cell surface receptors and signal via G-proteins
Proteins and Peptides
ACTH - corticotrophs
GH - somatotrophs
Prolactin - lactotrophs
Communication
Direct - neural to post. pit.
Indirect - vascular to ant. pit.
GnRh produces in parvocellular neurons and travels to ant.pit. in portal blood
Stimulates FSH and LH production
Hypophyseal portal system
Gonads
Different for males and females
Sex steroids and regulatory factors produced
Sex steroids
Progestagens
Pregnancy
Progesterone
17alpha-OHP
20alpha-OHP
Functions
Preparation of the uterus
Maintenance of the uterus during pregnancy
Growth of mammary glands
Suppression of lactation
Catabolic effects
Regulation of gonadotrophins
Receptors
PR-A
PR-B
All derived from cholesterol
Androgens
Male
DHT
Testosterone
Androstenedione
DHEA
Functions
Development and maintenance of the male reproductive system
Secondary sexual characteristics
Sexual function
Support spermatogenesis
Regulation of gonadotrophins
Receptors
AR - polymorphic with differing sensitivites to androgens
Oestrogens
Female
Oestradiol 17beta
Puberty to menopause
Oestriol
Pregnancy
Oestrone
Post-menopause
Functions
Secondary sexual characteristics
Stimulate growth and activity of mammary glands
Stimulation proliferation of endometrium for progesterone action
Regulate gonadotrophins
Receptors
ERalpha
ERbeta
Lipid soluble, act via steroid response elements (SREs)
Bound to carrier proteins
Albumin
Sex hormone binding globulin (SHBG)
Androgen binding protein (ABP)
Steroid action
Potency
Depends on affinity of steroid to receptor
Varies within each class
Cross-occupancy
Some bind receptors from other classes
Side-effects result
Some bind but don't activate
Antagonists
Regulation
Alter amount of steroid produced
Regulated by and regulate gonadotrophins of ant. pit.
Feedback loops
Alter amount or structure of receptor
Important in reproduction - gives better picture than hormone levels
Negative feedback in males, complicated feedback in females
Clinical aspects
Fertility
For females, endocrine problems are a common cause of infertility
Central Hypogonadism
Hypothalamus/pituitary problem
Low FSH/LH
Primary Hypogonadism
Ovary/testes problem
Lack of feedback
High FSH/LH
Prolactin
Inhibits HPG axis when in high doses
Levels increase in pregnancy and breast feeding
Inhibits gonadal activity through central suppression of GnRH
Induces lactational amenorrhea
The Menstrual Cycle
Cyclic gametogenesis, once per month
Hormonal changes cause folliculogenesis and endometrium changes
Three phases
Follicular/proliferative
Ovulation
Luteal/secretory
Duration
26-32 days
Follicular phase varies
Luteal phase
14 days
Fertile period
Oocyte - 24 hours
Sperm - 5 days
Oligomenorrhea
<9 cycles in last 12 months
Amenorrhea
No bleed in 6 months
Primary - since birth
Secondary - ceased
Menopause
Females - finite number of oocytes
Ovulation ceases around 50
Lack of progesterone/oestrogen production by ovary
Removal of -ve feedback leads to high FSH/LH levels
Higher FSH closer to menopause
Test for ovulation on day 21
Treatments/uses
Hormonal contraception
Synthetic progestagens and oestrogens
Suppress ovulation
Thickens cervical mucous
Thins endometrium
Fertility treatment
IVF/ICSI
Down-regulate HPG axis with GnRH agonist/antagonist, stimulate with FSH, induce oocyte maturation with hCG
Prostate cancer treatment
GnRH agonists suppress T cell production
Media attachments
Hypophyseal_portal_system (image/jpg)
sex_steroids (image/png)
HPG_Axis.PNG (image/PNG)
menstrual_cycle (image/jpg)
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