Repro Session 2 Flashcards
What does the HPG axis regulate?
Development, reproduction, ageing and other body processes such as somatic growth, water metabolism and lactation
What does the output of the HPG axis regulate the function of?
Thyroid, adrenal and reproductive glands
What is the contents of the neural stalk?
Hypothalamic neurons, superior hypophyseal artery and hypophyseal-portal circulation
Which peptide hormones does the anterior pituitary secrete?
Prolactin, ACTH, LH, GH, FSH, TSH and MSH
Where does the anterior pituitary arise from?
Rathke’s pouch
What regulates the anterior pituitary gland?
Hypothalamic hypophysiotropic releasing hormones via the hypophyseal circulation
Which it pituitary gland stains darker on histology?
Anterior
What connects the anterior pituitary to the hypothalamus?
Superior hypophyseal artery
Describe the action of hypothalamic releasing hormones.
Secreted in pulses tied to circadian rhythm and environmental factors to act in specific membrane receptors and activate second messengers
What is the result of activation of second messenger hormones by hypothalamic releasing hormones?
Stimulate synthesis and release of stored pituitary hormones, stimulate hypertrophy and hyperplasia of target cells and regulate own receptors
Which hypothalamic releasing hormones are associated with each anterior pituitary peptide hormone?
Prolactin: stimulated by PRH and TRH, inhibited by dopamine
GH: stimulated by GHRH and inhibited by somatostatin
ACTH: CRH
FSH: GnRH
LH: GnRH
TSH: TRH
Which cells release each of the anterior pituitary peptide hormones?
Prolactin: mammotropic GH: somatotropic ACTH: corticotropic FSH: gonadotropic LH: gonadotropic TSH: thyrotropic MSH: pars intermedia
What is the posterior pituitary gland?
Neurosecretory gland that is an outgrowth of the hypothalamus that secretes ADH and oxytocin
Describe the hypothalamic control of FSH and LH.
GnRH released ~1x per hour into portal circulation –> GPCR on gonadotrophs activated to produce LH and FSH –> GsPCR of gonads stimulates adneylate cyclase –> granulosa and theca interna activated or Sertoli and leydig cells activated providing negative feedback via oestrogen, progesterone and inhibin
How does negative feedback on the anterior pituitary arise?
Gonadal hormones affect the stimulating ability of GnRH
What are the results of cell stimulation by the HPG axis at the gonads?
Ovulation, folliculogenesis, steroidgenesis and spermatogenesis
What percentage of total anterior pituitary cells do gonadotrophs account for?
5-10%
Do gonadotrophs produce LH and FSH simultaneously?
Most yes but a small subpopulation only release exclusively either
Which hormones descrease GnRH secretion?
Testosterone, moderate titres of oestrogen, progesterone
What do high titres of oestrogen alone cause?
Promotion of GnRH secretion and subsequent LH surge
How does the inhibitory action of oestrogen at low titres and progesterone on GnRH release differ?
Oestrogen decreases amplitude of pulse, progesterone decreases frequency
What is secreted by the gonad in both sexes in relation to developing gametes to selectively reduce FSH secretion?
Inhibin
What is the action of testosterone?
Promotes spermatogenesis
What is the action of androgen binding globulin?
Bind to testosterone and keep it in the seminiferous tubules
What is the role of inhibin?
Support spermatogenesis and control HPG axis
What do leydig cells secrete?
Testosterone
What do Sertoli cells secrete?
Androgen binding globulin and inhibin
What is the action of theca cells in the HPG axis?
Secrete androgens that granulosa cells can convert to oestrogen to regulate axis
Which cells release inhibin in the female?
Granulosa
Why is an additional stage to oestrogen control needed in the female HPG axis?
Because oogenesis is cyclical
Why must hormones in the male HPG axis be constant in the medium and long term?
Because spermatogenesis occurs continuously so the male reproductive fact must be continuously ready for action
What happens to inhibin if the rate of spermatogenesis increases?
More is released to reduce FSH
What effects does testosterone have?
Determinative: irreversible secondary sexual characteristics and regulatory effects to maintain adult repro system
Why are male hormone levels not constant in the short term?
Follow circadian rhythm so testosterone is highest in the morning and when environmental stimuli drive the brain
What do hormones of the HPG axis control?
Fertilisation, support of conceptus, embryo and foetus, birth at the right time and support of the neonate
Why is +ve feedback seen in the female HPG axis?
To regulate ‘waiting phase’ needed to prepare for implantation should fertilisation occur
What stages does the menstrual cycle broadly consist of?
Preparation of gamete by ovarian cycle and endometrium by uterine cycle, ovulation and waiting
Describe the start of the menstruated cycle.
Cell death has occurred so hormones are at baseline, early development of follicles begins giving low level steroids and inhibin, little HPG inhibition so FSH rises and binds with granulosa cells –> oestrogen production
What does the primordial follicle develop independent of?
Signals outside gonad
What does oestrogen production depend on the interplay of?
Granulosa and theca interna cells
What happens in the mid follicular phase of the menstrual cycle?
Specific inhibition of FSH by inhibin (inhibiting activin at anterior pituitary) so dominant follicle can develop, follicular [oestrogen] exerts +ve feedback and LH rises
What happens in the mestrual cycle during preparation for ovulation?
Circulating inhibin and oestradiol levels increase rapidly, oestrodiol production is no longer dependent on FSH, theca and granulosa cells express LH receptors and progesterone production begins to moderate GnRH pulses. LH surge
What layers is the endometrium divided into?
Zona compacta, zona spongiosa and zona basalis
What causes menses?
Sudden drop in progesterone causes ischaemia of spiral arteries in the upper layer of the endometrium –> necrosis of functionalis layer
What are the 3 stages of the endometrial cycle?
Menses, proliferative and secretory
What are the 3 phases of the ovarian cycle?
Follicular, ovulatory and luteal
Which endometrial and ovarian phases correlate?
Proliferative and follicular, secretory and luteal
What halogens during the LH surge?
In the late follicular phase high [oestradiol] enhances sensitivity of gonadotrophs to GnRH –> high amplitude peaks in LH
What causes high [oestradiol] in the late follicular phase?
Lots of granulosa and theca interna cells interacting
What happens during ovulation in the menstrual cycle?
Meiosis I completes and meiosis II starts, LH is dominant and exerts indirect effects on the oocyte via corona radiata cells, mature oocyte –> ovary capsule
How is the waiting phase of the menstrual cycle established?
Follicle lutenised, secreting lots of oestrogen and progesterone due to LH on granulosa cells which is inhibited by progesterone, inhibin production continues and further gamete development is suspended
What characterises the luteal phase of the menstrual cycle?
Presence of corpus luteum
What is the corpus luteum?
Highly endocrine organ that produces progesterone and oestrogen from androgens whilst the theca cells thicken and become hyperaemic
What does corpus luteum inhibin production promote?
Progesterone release
What happens to the corpus luteum if there is no subsequent rise in LH?
Spontaneous regression
Describe the pathway at the end of the menstrual cycle if there is no second surge in LH.
Corpus luteum undergoes apoptosis –> dramatic fall in gonadal hormones –> -ve feedback relieved –> cycle resets and tissues developed are lost
Describe the pathway at the end of the menstrual cycle of fertilisation occurs.
Syncytiotrophoblast produces hCG that exerts a lutenising effect –> second surge in LH and corpus luteum is maintained
How does hormonal control of the HPG axis change during pregnancy?
Initially placental hCG supports corpus luteum to produce steroid hormones but eventually the placenta can take over steroid hormone production
How does basal body temperature change during the menstrual cycle?
Lower in follicular, higher in luteal, drops just before ovulation
What are the actions of oestrogen in the follicular phase?
Fallopian tube function, thickening of endometrium, growth and motility of myometrium, thin alkaline cervical mucus, vaginal changes and changes in skin, hair and metabolism
What are the effects of progesterone in the luteal phase?
Thickening of endometrium to secretory form, thickening of myometrium but decreasing its motility, thick acid mucus to prevent polyspermy, changes in mammary tissue, increase in body temperature and metabolic and electrolyte changes
What is the normal duration of the mestrual cycle?
21-35 days
What are variations in length of the menstrual cycle due to?
Variations in follicular phase as the luteal phase is strictly controlled at 14 +/- 2 days
What external factors to the HPG axis can cause a decrease in GnRH pulse frequency?
Emotional stress and low body weight