Jones - taught Flashcards
What is the HPG axis
The hypothalamic–pituitary–gonadal axis
multiple endocrine glands working together as a system
What does the HPG axis do?
regulate development, reproduction, and ageing in animals
What do endocrine glands do?
secrete hormones into the bloodstream; the hormones travel to and act on other organs or tissues
What are the components of the HPG?
- Hypothalamus
- Anterior pituitary
- Testes/ovaries
What is the hypothalamus?
Component of forebrain; part of the diencephalon
What does the hypothalamus do?
Regulates many core body functions (homeostatic functions) eg. Metabolism, growth, reproduction, stress.
How is the hypothalamus in contact with the anterior pituitary gland?
Secretes a peptide hormone: gonadotrophin releasing hormone (GnRH)
Critical component of the reproductive system
What are the two parts of the pituitary gland?
• Posterior and anterior (distinct lobes); derived from separate types of cells during embryogenesis; different functions.
What is the anterior pituitary gland?
An endocrine gland
What is the anterior pituitary gland made up of?
different groups of cells: o Thyrotropes (Thyroid-stimulating hormone; TSH) o Somatotropes (Growth hormones) o Gonadotrophs (Follicle-stimulating hormone; FSH and Luteinising hormone; LH) o Corticotropes (adrenocorticotropic hormone; ACTH) o Lactotropes (prolactin; PRL)
How does GnRH connect the three systems?
GnRH from the hypothalamus travels in the portal blood to the anterior pituitary where it acts on gonadotrophs
How does GnRH positively regulate cells proliferation and hormone production?
through a G-protein-coupled receptor (GnRHr)
What does GnRHr signalling stimulate?
Production of FSH and LH
What is GnRH?
short polypeptide
What do FSH and LH do?
act on different types of cells and these cells ten produce different hormones
What are the three main types of sex steroid?
progestagens, androgens and oestrogens
What are sex steroids derived from?
a common precursor: cholesterol
Interconversion of sex steroids is via?
a biosynthetic network
Action of these steroids is dictated by tissue-specific receptors
T
Once inside a cell a steroid …
steroid-receptor complexes bind to steroid response elements on DNA and impact on transcription
What affect does oestrogen have on gonadotrophs?
- Oestrogen binds to the oestrogen receptor (ER) on the gonadotroph
- The hormone-receptor complex translocates to the nucleus and mediates negative transcriptional control of target genes through oestrogen response elements (EREs)
- Suppression of transcription
- This regulates the production of FSH and LH
What family are th inhibins and activins from?
TGFβ
What do inhibins/activins do on gonadotrophs?
bind to inhibin and activin receptors on the gonadotroph cell
They act to regulate FSH and LH expression
What is LH and FSH output predominantly regulated by in females?
secretory products from the ovary
In females Negative feedback on LH and FSH is by?
: oestrogens, progestogens and inhibins
in females Positive feedback on LH and FSH is by?
activin; oestradiol (an oestrogen)
What is the effect of oestradiol in females?
at low concentrations acts to negatively regulate LH expression but at high levels it acts to positively regulate expression
What is the effect of progesterone in females?
o High concentration seen in luteal phase of menstrual cycle (after ovulation) enhances the negative feedback of oestradiol
o At certain levels, the positive feedback effect of oestradiol is blocked
What level does feedback act on the HPG axis?
both the levels of the pituitary and at the level of the hypothalamus
How do the waves affect the hypothalamus?
both the magnitude and frequency of the waves
Do you get positive feedback at the male HPG axis?
No as don’t need a cycle as in females
What do Leydig cells secrete?
androgens
What do androgens do in males?
exerts a negative feedback response which causes decrease in GnRH
What level do inhibins act at in both males and females?
the level of pituitary to supress FSH secretion
How is GnRH secretion regulated?
release is pulsatile - begin at puberty
Pulse generator resides in hypothalamus
Increasing or decreasing the amplitude or frequency of GnRH pulses
What is Kisspeptin?
Master player of control of reproduction
54 amino acid neuropeptide
encoded by KISS1
What is the function of Kisspeptin?
It binds to the receptor 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
What is leptin?
peptide hormone produced by adipocytes
May be involved in activating the HPG axis at puberty via KISS1
Relationship between weight and fertility
How is there Interplay of leptin and kisspeptins in controlling puberty onset?
puberty is metabolically gated
Kisspeptins are essential upstream regulators of GnRH neurones
Leptin is necessary for puberty to proceed, but is not the sole requirement
Leptin acts on GnRH neurones indirectly via other neurons)
• Some evidence suggests that leptin acts via the Kiss1 neurons
What are the organs of the male reproductive system?
- Testes
- Epididymis
- Vas deferens
- Seminal vesicle
- Prostate gland
- Urethra
What is the function of the testes?
Houses seminiferous tubules; site of spermatogenesis.
What is the function of the Epididymis?
Sperm storage and maturation.
What is the function of the Vas deferens?
Transport of sperm from epididymis to urethra during ejaculation.
What is the function of the seminal vesicle?
Produces a mucus secretion which aids the mobility of sperm.
What is the function of the Prostate gland?
Produces an alkaline secretion that neutralises acidity of any urine in the urethra and aids the mobility of sperm.
What is the function of the Urethra?
Tube that carries urine and sperm out of the body
What are the two functions of the testis?
- To produce androgens and other hormones for sexual differentiation
- To produce spermatozoa for sexual reproduction
Where in the testis are steroid hormones synthesised?
Leydig cells
Where are spermatozoa produced?
in the seminiferous tubules with maturation in the epididymis
What are Primordial germ cells?
PGCs are the gamete precursors.
How does the PGC population exand?
By mitosis
Where do the PGCs migrate to?
the genital ridge primordium or in and become sertoli of granulosa cells
How do environmental factors influence PGCs?
can lead to infertility
Overview of spermatogenesis
- Begins at puberty; about 100 million produced per day
- Involves mitosis and meiosis
- Undergo two rounds of meiosis and become 4 spermatids
- Final differentiation step is called spermiogenesis and makes spermatazoa
- Generates four mature spermatozoa – identical in size but not genetically
What are spermatogonial stem cells (SSCs)
- SSCs self-regenerating pool undergo rounds of mitosis
* At intervals, groups of morphologically distinct cells emerge
What influences the SSCs decision to divide or differentiate?
Growth factors
Process of spermatogenesis
Development occurs in centripetal direction – from the outside towards the lumen of the seminiferous tubules
Mature sperm are next to the lumen where they are released
What is spermiation?
the cytoplasmic bridges are broken and mature sperm can be released
What is the sperm morphology?
Highly differentiated head containing nucleus
Acrosome cap; important for fertilization
Tail required for motility
Mid-piece contains the mitochondria
Central axoneme made up of bundles of fibres; allows tail movement
Sperm head shape differs between species
process of Spermiogenesis?
Golgi apparatus forms the acrosome cap
Genetic material is really condensed – nucleus changes shape to fit into the sperm head
One of the centrioles of the spermatid elongates to become the tail
The remaining cytoplasm and organelles (residual body) are removed by Sertoli cells via phagocytosis
How is the chromatin remodelled?
- X and Y chromosome transcription stops before meiotic divisions
- Autosomal transcriptional activity ceases later, during spermiogenesis
- Massive repackaging of the DNA: histones are replaced by protamines; tightly compressed chromatin with no gene expression
What are sertoli cells?
somatic cells