Reproductive hormones and the HPG axis Flashcards
Name the different types of hormone signalling
- Endocrine
- Paracrine
- Neuro-endocrine
- Autocrine
- Neural
Describe endocrine signalling
Delivered to blood to get to remote site of action (not every cell in teh body will have the necessary receptors for every hormone)
Describe paracrine signalling
Does not require systemic blood flow, passed through interstitial flow
Describe neuro-endocrine signalling
Hormone passed into blood from neurone to be passed to the target cell
Describe neural signalling
Neurone produces active substance and delivers to target cells without circulation
Explain the importance of hormone receptors for hormone signalling
- Receptors are expressed by target cells and are specific to a hormone
- No receptor = no response
- The ligand (hormone) will bind to or “fit” a site on the receptor
- Have to bind to carry out function
Describe lipid soluble hormones (give examples)
- Must be transported in blood by carrier proteins
- May be specific to the hormone or general bulk carriers
- Diffuse through plasma membrane and bind to intracellular receptors
- Alter expression of genes at level of nucleus
- e.g. steroid hormones
Describe water soluble hormones
- Easily travel in blood
- Excluded from cells by lipid bilayer
- Bind to receptors on surface of cells
- Results in series of intracellular events
- e.g. GnRH, FSH, LH, IGF
Describe peptide hormones
- Work at cell surface
- Result in second messenger signalling
- Peptie can be considered priamry messenger
- Binding leads to cascade of enzymatic actions
Describe steroid hormones
- Not received at cell surface, pass through plasma membrane into cytosol
- Bind to intracellular receptors
- Receptor-hormone complex into nucleus to act on DNA
- Slower rate of action (more needs to happen before get a response)
What reproductive hormones are produced by the hypothalamus?
GnRH
What reproductive hormones are produced by the pituitary?
- ADH, chorionic gonadotrophins (FSH and LH) from anterior pituitary
- Prolactin from ant pit
- ## Oxytocin from post pit
Where is oxytocin synthesised?
Hypothalamus
What reproductive hormones are produced by the ovary?
- Oestrogens
- Progesterone
- Inhibin
- Oxytocin
- Relaxin
- Some testosterone
What reproductive hormones are produced by the testes
- Testosterone and other androgens
- Inhibin
- Oestrogen
What reproducive hormones are produced by the placenta?
- Prostaglandin F2alpha (PGF2a)
- Progesterone
- Oestrogen
- eCG and hCG (equine and human chorionic gonadotrophins)
Describe the structure of gonadotrophins
- Formed of standard alpha subunit and varying beta-subunits
- Glycoprotein heter-dimers with shared alpha chain
- Different beta-chain depending on which gonadotrophin
Describe the gonadotrophin receptors
- Act on G-protein-7-transmembrane receptors
- LH and chorionic gonadotrophs bind a common receptor
What has to happen to gonadotrophins before excretion?
A series of metabolic conversions
Describe the synthesis of steroids
- From dietary cholesterol thorugh series of enzymatic conversions
- e.g. testosterone to oestradiol via aromatase
- All have similar structure
How are steroids inactivated and where?
- Liver, 2 ways
- Saturation of all double bonds = inactivated
- Sulfate or glucuronide attached making it water soluble allowing excretion in urine as glucuronide or sulfate salt
How is progesterone inactivated?
Saturation of all double bonds
How is testosterone inactivated
Formation of glucuronide or sulfate salts
Describe the main features of prostaglandins
- Synthesised from arachidonic acid
- High levels in seminal fluid
- At least 6 biocehmical PGs and many metabolites
- Bind to cell memrbane G protein coupled receptors- 2 importna tin repro: PgF2a and PGE2
- Rapidly degraded (seconds, single passage through pulmonary system)
Describe the hypothalamic pituitary gonadal axis in general
- Hypothalamus released GnRH, acts on pituitary to stimulate release of LH and FSH, act on the gonads
- Have feedback loops throughout the HPG axis
Describe the input of the CNS to the HPG axis
- Information on physical and environmental state
- Pheromones, tactile, visual reaction to bellowing of animal etc
- Stimulates the hypothalamus
What are the 2 GnRH rich areas of the hypothalamus in the male?
- Optic chiasma
- Paraventricular nucleus
What is the connection between the hypothalamus and the anterior pituitary?
- Hypothalamo-hypophyseal-poral system
- 2 vascular networks in series
- Primary portal plexus in the stalk areas, down into the secondary portal plexus
Describe the function of the hypothalamic-hypophyseal-portal system
- Neurones from hypothalamus to portal plexus, release small amounts
- Ok to be small amounts as not diluted by circulation
- Transports GnRH from hypothalamus to ant. pit.
- Neurohormones diffuse out, bind to receptors on endocrine cells
- Stimulate release of LH and FSH
Describe the connection between they hypothalamus and the posterior pituitary
- Neuronal connection
- Release into post. pit for storage and then secretion from there to target cells via blood
Describe the Leydig cells
- LH receptor
- Testosterone production
- Outside of seminiferous tubules
Describe the Sertoli cells
- FSH receptors
- Produce inhibin
- Found within seminiferous tubules
What is the effect of testosterone on the hypothalamus?
Inhibitory to GnRH release
What is the effect of testosterone on its target tissues?
Stimulatory
What is the effect of inhibin?
Inhibitory to the production of FSH and LH
What structures can be found within the ovary?
- Follicles (at various stages of development)
- Corpus luteum
Give a brief overview of the develoment and release of the oocyte in the ovary
- Primordial follicle to antral phase
- Dominant follicle ready for ovulation
- then release of oocyte
- Following release, follicle becomes corpus haemorrhagicum, then corpus luteum and regressing CL is corpus albicans
What is the function of the follicle?
- Oocyte development
- Multiple stages of development
- Oestradiol secretion
What is the function of the corpus luteum?
- Follows ovulation
- transient endocrine gland
- Progesterone secretion
Where is GnRH produced in the female?
- 2 groups of hypothalamic neurons
- surge (pre-ovulatory) centre
- Tonic centre
Describe the basal GnRH secretion
- Numberous small pulses, regular and brief
Describe the preovulatory surge of GnRH
- High levels of GnRH secretion for extended period of time
- Stimulated by increased oestrogen
What is the function of the pre-ovulatory surge?
Stimulates ovulation in the absence of progesterone
Briefly describe the HPO axis in females
- GnRH stimulates secretion of LH and FSH
- Stimule follicle to produce oestroadiol
- High levels has positive feedback, threshold reached and pre-ovulatory surge occurs
- Inhibin secreted from follicle, inhibitory to FSH
Explainthe FSH to LH shift at to ovulation
- Prior to ovulation FSH more dominant than LH
- Inhibin has negative feedback effect on FSH
- Nearer to ovulation follicle depends more on LH than FSH (as FSH is being inhibited)
Briefly describe the hormonal events at ovulation
- Dominant folllicle producing oestradiol
- GnRH stimulates LH surge
- Leads to ovulation
- Following ovulation get early CL which produces progesterone
What is the function of the progesterone produced by the CL?
- Negative feedback to GnRH
- Prevents follicle development, oestradiol production, oestrus and GnRH/LH surge
- Positive actions on mammary gland and endometrium (preparation for pregnancy)
- Inhibits myometrium
- Inhibits ovulation
Briefly describe luteolysis
- Stimulated by PGF2a from uterus
- Rapid deteriation of CL
- Progesterone removed