Lecture 3 - Menstrual cycle I Flashcards
Menstrual cycle: what processes does it underdo?
- Maturation of the female gamete (oocyte) in the ovary and its transport to the site of fertilisation (uterine tube, aka Fallopian tube or oviduct)
- Preparation of the uterine endometrium as a suitable site for implantation of a developing embryo
- Menstruation if no embryo implanting occurs
HPG axis: what is it and what is the process?
hypothalamic-pituitary-gonadal axis
- Kisspeptin neurons activate gonadotrophin-releasing hormone (GnRH) neurons in the hypothalamus
- Hypothalamus releases gonadotrophin releasing hormone (GnRH)
- GnRH causes Gn release (FSH/LH) from the anterior pituitary
- FSH/LH affect the ovaries and cause oocyte development and ovulation
Menstrual cycle: what two parts of it are there?
- Uterine cycle
- Ovarian cycle
Uterine cycle
- Menstrual phase - ~5 days
- Proliferative phase - ~9 days
- Secretory phase - ~14 days
Ovarian cycle
- Follicular phase - ~14 days
- Luteal phase - ~14 days
Why does the uterus lining break down?
The lack of circulating progesterone
What follows the drop of circulating sex hormones?
FSH levels start to rise - this is due to the decreased amount of negative feedback on the hypothalamus and anterior pituitary
FSH: what is it, what produced it, and what does it do?
Follicle stimulating hormone
The hypothalamus/anterior pituitary
Causes maturation of secondary follicles into tertiary follicles
Follicles: what are they, how does their maturation work, and what hormone do they produce?
Small sacs found in the ovaries that contain eggs
- Ovaries enter the follicular phase as the uterus layer breaks down - results in maturation to secondary follicles
- Maturation to tertiary follicles arises in the presence of FSH
Oestrogen
What causes the shift from the menstrual phase to the proliferative phase of the uterus?
Circulating oestrogen arising from tertiary follicles
Circulating oestrogen: does it undergo negative or positive feedback and why?
It undergoes negative feedback unless a threshold is reached, at this point positive feedback occurs and a rise in FSH and LH occurs
Follicular phase of the ovaries: how long does it last, what causes progression into this phase, and what does it do?
~14 days
Menstruation
Matures follicles until a dominant follicle is ready to be released
Luteal phase of the ovaries: how long does it last, what causes progression into this phase, and what does it do?
~14 days
Release of the egg from the follicle
Produces oestrogen and large amounts of progesterone - builds up and maintains the uterus lining
Menstrual phase of the uterus: how long does it last, what causes progression into this phase, and what does it do?
~5 days
Lack of fertilised egg binding to uterus
Breaks down the lining of the uterus, including many cell types
Proliferative phase of the uterus: how long does it last, what causes progression into this phase, and what does it do?
~9 days
Circulating oestrogen produced by follicles
Builds up the lining of the uterus
Secretory phase of the uterus: how long does it last, what causes progression into this phase, and what does it do?
~14 days
Circulating progesterone produced from the luteal phase of the ovaries
Endometrial secretions occur which support an embryo until it is ready for implantation
Estrous cycle: what is it and how does it operate in animals and humans?
Behavioural strategy to ensure mating occurs at time of ovulation
Animals:
* Sexual stimulus
* Accept advances more readily
* Enticing behavioural gestures
Humans:
* Men prefer the smell of women in the middle of their menstrual cycle - sexual stimulus?
* Provocative movements potentially?
* Androstenone better tolerated
Puberty: what controls it
- Genetic
- External factors - adiposity, endocrine disrupting chemicals, intra-family relationships, stressful events, etc
Adiposity: why is it suggested to affect puberty age?
- Puberty age has decreased over time
- Countries with sub-optimal socioeconomic status have puberty later
- Delayed puberty in malnutrition and low weight
- Moderate obesity is associated with advanced puberty
Adiposity: by what mechanisms may it affect puberty age?
Leptin?
Adipose tissue may cause leptin secretion which binds to LepR in gonadotrophin releasing hormone (GnRH) neurones in the hypothalamus
This is wrong - GnRH neurones don’t express the leptin receptor
Kisspeptin?
This is regulated by leptin and fills the gap in the previous model - leptin stimulates kisspeptin neurones which secrete kisspeptin which binds to GnRH neurones which can then cause gonadotrophin release from the anterior pituitary
Kisspeptin: what is it, where is it produced, what does it do, what is it regulated by, and what is its potential pathway for inducing puberty?
GPCR ligand
Produced in the hypothalamus:
* Arcuate nucleus - important in GnRH pulse generation
* Anteroventral periventricular nuclei - GnRH/LH surge and ovulation
Leptin
Leptin stimulates kisspeptin neurones which secrete kisspeptin which binds to GnRH neurones (GPR54) which can then cause GnRH release - this then reaches the anterior pituitary and causes Gn release
What evidence suggests kisspeptin plays a role in puberty age?
Disruption of the gene results in failure of sexual maturation but treatment of juvenile rats with kisspeptin advances puberty timing
GnRH: what is it, what is its structure, what does it do, and what types of GnRH release are there?
Gonadotrophin releasing hormone
Simple amino acid structure (10 aa’s)
Acts as a ligand for the GnRHR which signals through Gαq and PLC to result in transcription of Gonadotrophins
Pulses or surges
GnRH pulses: why are they important and what do they do?
Promote the production of FSH
GnRH surges: why are they important and what do they do?
Promote the production of LH
FSH: what is it, what is its structure, what confers its specificity, what is its production stimulated by, where is it secreted from, and where is it packaged within the cell?
Follicle stimulating hormone
Dimeric protein with both an α and β subunit (α identical in LH)
β subunit
Slow pulses of GnRH
Anterior pituitary
Secreted through the constitutive pathway - little storage within the cell
LH: what is it, what is its structure, what confers its specificity, what is its production stimulated by, where is it secreted from, and where is it packaged within the cell?
Luteinising hormone
Dimeric protein with both an α and β subunit (α identical in FSH)
β subunit
Fast pulses of GnRH
Anterior pituitary
Packaged in electron-dense granules, in association with storage protein secretogranin II
How are FSH/LH secretions regulated?
- GnRH binds to GnRHR
- Causes activation of Gαq
- Gαq activates PLC
- PLC activates protein kinase C - PKC activated MAPK, promoting βLH, βFSH, and FSH/LHα subunit production
- FSH is dimerised then constitutively released
- LH is packaged near to the PM, often on cells near capillaries- secretion is activated by Ca²⁺ ??????????
GPCRs: what are they, what do they do, what is their structure, and how many domains do they have?
G protein-coupled receptors
Bind with ligands, activating their attached G protein which can then do downstream signalling
Long protein that passes through the membrane (7 times) and has extracellular/intracellular compartments
Ectodomain (NH₂), transmembrane, and cytoplasmic domain (COOH)
G proteins: what are they, what is their structure, how do they become activated, and how many α subunit families are there?
Guanine proteins
Heterotrimer - αβγ subunits
GPCRs induce a conformational change in the α subunit, causing a swap of GDP to GTP and α subunit dissociation
Gαq - activates phospholipase C
Gαs - activates adenylate cyclase
Gαi - inhibits adenylate cyclase
Gα12 - Rho family of GTPases
PLC: what is it, what is its function, and what is its pathways?
Phospholipase C
Causes downstream signalling after being activated by Gαq
- Converts PIP₃ into PIP₂ and IP₃ which binds to receptors on the ER and Ca²⁺
- Activates PKC which causes activation of the MAPK pathway
FSH/LH receptors: what G protein are they coupled to, what is activated, and what is the downstream signalling?
Gαs
Activated adenylate cyclase
- Causes conversion of ATP to cAMP
- cAMP caused activation of PKA
- PKA phosphorylates of Ser/Thr motifs
