The HPG axis Flashcards
What is HPG?
The hypothalamic-pituitary-gonadal axis
What is the HPG axis part of?
The endocrine system
What do endocrine glands do?
Endocrine glands secrete hormones into the bloodstream; the hormones travel to and act on other organs or tissues
Describe the axis? And what does this include?
Axis: multiple endocrine glands working together as a system to regulate development, reproduction, and aging in animals.
Hypothalamus
Anterior pituitary
Testes/ovaries
Describe the position hypothalamus
Component of forebrain; part of the diencephalon
Hypothalamus is in contact with the anterior pituitary gland
Function of the hypothalamus
Regulates many core body functions (homeostatic functions) eg. Metabolism, growth, reproduction, stress.
Secretes a peptide hormone: gonadotrophin releasing hormone (GnRH; 10aa long)
What is the pituitary glad composed of?
Posterior and anterior; derived from separate types of cells during embryogenesis; different functions.
Describe the anterior pituitary gland
Anterior pituitary is an endocrine gland.
Made up of different groups of cells:
Thyrotropes (Thyroid-stimulating hormone; TSH)
Somatotropes (Growth hormones)
Gonadotrophs (Follicle-stimulating hormone; FSH and Luteinising hormone; LH)
Corticotropes (adrenocorticotropic hormone; ACTH)
Lactotropes (prolactin; PRL)
Where does GnRH travel?
GnRH from the hypothalamus travels in the portal blood to the anterior pituitary where it acts on gonadotrophs
What does GnRH binding result in?
GnRH binding results in a signalling cascade culminating in expression of luteinising hormone (LH) and follicle-stimulating hormone (FSH), both heterodimeric glycoprotein hormones
What do Gonadotroph cells release?
Gonadotrophs release LH and FSH for transport to the ovaries and testes via the bloodstream
Gonadotrophs are specialized cell types of the anterior pituitary that synthesize and secrete LH and FSH.
What does GnRH stimulate?
GnRH stimulates gonadotrophin proliferation and hormone production via GnRHr receptor
The HPG axis
Diagram…
What are the three main sex steriods? Give examples…
Three main types of sex steroid: Progestagens (e.g. progesterone),
Androgens (e.g. testosterone; dihydrotestosterone; androstenedione)
Oestrogens (e.g. oestradiol; oestrone)
Descrobe sex steriods
All derived from a common precursor: cholesterol
Interconversion occurs via a biosynthetic network; enzymatic defects at a single point in the network can have far-reaching effects
Action of these steroids is dictated by tissue-specific receptors
Once inside a cell, steroid-receptor complexes bind to steroid response elements on DNA and impact on transcription
The sex steroids are essential for normal reproductive development, gametogenesis and the maintenance of secondary-sex characteristics
How do the three sex steriods play a major role?
Progesterone (P), Testosterone (T) and Oestrogen (E) play major feedback roles via action on pituitary gonadotrophs
What to the sex steriods do once theyve entered a gonadotroph
What does this regulate?
The hormones enter the cell and combine with their receptors. Hormone-receptor complexes translocate to the nucleus and mediate negative transcriptional control of the target genes
This regulates the production of FSH, LH and also the GnRH receptor, thus reducing gonadotroph stimulation from the hypothalamus
What do male and female gonadal cells express? Describe cascade of events
Male and female gonadal cells also express Inhibin and Activin, members of the transforming growth-factor-β (TGF-β)) family
They bind to Inhibin and Activin receptors on the gonadotroph cell
They exert opposing actions on FSH expression. Inhibin also binds to Activin to modulate its activity
Both protein families have other diverse biological roles e.g. germ cell development; tumour suppression; erythropoiesis
WHat is GnRH essential for?
GnRH is essential for gonadal function: destruction of GnRH neurons, generation of genetically null GnRH mice, or immunisation against the GnRH peptide all result in gonadal atrophy
GnRH release
GnRH release is pulsatile (~1 per hour). GnRH pulses begin at puberty. Pulse generator resides in hypothalamus
How are anterior pituitary hormones released?
Anterior pituitary hormones are also released in a pulsatile manner in post-pubertal humans. Very little is released before puberty
How can alterations in the output of LH and FSH be achieved?
Alterations in the output of LH and FSH can be achieved by:
Increasing or decreasing the amplitude or frequency of GnRH pulses
Modulating the response of the gonadotrophs to the pulses
How is GnRH secretion regulated?
What is RFRP-3?
Kisspeptin: master player of control of reproduction; 54 amino acid neuropeptide (encoded by KISS1)
It binds to the GPR54 receptor (or KISS1R) found in GnRH neurons; Kisspeptin is a potent GnRH stimulator
KISS-1 +ve neurons are direct targets of oestrogens. Binding of oestrogen results in negative feedback by decreasing GnRH expression
RFamide-related peptide 3 (RFRP-3) is a mammalian orthologue of Gonadotropin-inhibitory hormone (GnIH).
It acts on the gonadotrophs, kISS-1 neurons and GnRH neurons in the hypothalamus. It results in reduced GnRH output and also suppresses the signalling cascade within gonadotrophs that are responsible for LH and FSH expression
Whats the potential function of kisspeptin neurons
Mediating the relationship between enegry balance and reproduction
