TOPIC LIST 1 – REPRODUCTIVE PHYSIOLOGY, PHARMACOLOGY AND GENERAL PATHOLOGY; SMALL RUMINANT REPRODUCTION Flashcards
Hypothalamus & Hypothalamic Hormones
Cell bodies of hypothalamic neurons form nuclei, and can be characterised by the NT they produce
Important to reproductive physio;
N. paraventricularis and n. supraopticus - oxytocin
N. arcuate and n. ventromedialis - GnRH
Physiology of GnRH (Gonadotropin-releasing hormone) Secretion
GnRH:
• A trophic (deca)peptide hormone synthesised and released by the hypothalamus
• Responsible for the release of FSH and LH from the pituitary (GnRH constitutes the first
step in the hypothalamic-pituitary-gonadal axis)
• It is 1183 Da in size and has a short T1⁄2 (max. 1.5-2 mins)
Secreted GnRH then reaches a vascular network (portal plexus/portal venous system), which transports GnRH to the anterior pituitary.
Tonic Centre
Located ventrally on the hypothalamus, N. Arcuate & ventromedialis , on either side of the third ventricle
o GnRH is released constantly but at a low frequencyàThe tonic centre is
responsible for the basal secretion of GnRH
o Tonic centre neurons are active in both sexes, and release GnRH in regular, brief
pulses (approx. every 2-3 mins)
o Little/∅ secretion before puberty
o Amplitude and frequency of secretion pattern is species-specific (pattern can be
seen when measuring GnRH conc in portal vessels of the hypothalamus) o Induces LH release after approx. 20 mins
o More freq. GnRH pulses à More freq. LH pulses
Surge Centre
Anterioir hypothalamic region, pre opitic area
o Only releases GnRH following a strong stimulus (, but release GnRH with a much
higher frequencyàHigher concentration of GnRH in the portal plexus
o In females, small quantities of GnRH are released, until stimulated by rising
concentrations of oestrogens in the blood (+ve feedback of oestradiol)à Circulating oestrogen conc. reaches a threshold level, prior to ovulation, resulting in large-scale GnRH release (‘GnRH surge’)
o A corresponding peak in LH secretion follows this GnRH surge à Pre-ovulatory LH peak
o Sensitivity to of the surge centre to E2 is the key factor in ovarian cyclicityà Insensitivity in the surge centre to E2 = ∅ ovulation
o In males the surge centre is inactivated during early foetal life
Tonic and surge centres in males
N.B. in males there is no functional difference between the two centres (i.e. both work as a tonic
centre)àSexual dimorphism in the brain.
Testosterone is produced by foetal testicles and crosses the BBB where it is converted to oestradiol by neuronal aromatase. Because of the presence of E2, neurons of the surge centre do not properly develop and ∴ become insensitive to E2-induced +ve feedback. (In females, oestradiol levels are higher but are strongly bound to α-foetoprotein in the blood and cannot reach the CNS, i.e. it is the presence/absence of E2 within the CNS which is responsible for sexual dimorphism in the brain)
Hormonal profiles differ between the sexes due to the consequences of prenatal ‘defeminisation’ of the brain.
GnRH pulse frequency
The change in GnRH pulse frequency determines the rate of FSH and LH release from the hypophysis:
• Low GnRH pulse frequencyàFSH production > LH production
• High GnRH pulse frequencyàLH production > FSG production
Regulation of GnRH secretion
Internal stimuli
Blood concentrations of oestrogen (E2), progesterone (P4) and testosterone
• High concs of testosterone and P4 inhibit GnRH secretion
• High concs of oestradiol during the follicular phase in females
stimulates GnRH secretion
Environmental stimuli
Stress, photoperiod, olfactory stimuli (e.g. pheromones) etc.
Role of GnRH
GnRH controls the release of gonadotrophins (FSH and LH) from gonadotroph cells in the anterior pituitary.
The hypothalamus is not the only factor responsible for regulating FSH and LH release:
• Females – Inhibin is secreted by developing follicles, inhibiting FSH secretion from the
anterior pituitary
• Males – Inhibin is secreted by Sertoli cells in the testes
Oxytocin
prod by hypothalamus, N. paraventricularis and supraopticus
SM contraction, targets ReproTract
role in milk ejection reflex
Infleunces libido, social and maternal behaviour
Blood level is higher in females, except during orgasm, marked increase in both sexes
Pituitary gland
located ventral to the hypothalamus, ant and post lobes
Ant. Lobe
- gonadatorps cells produces FSH and LH (under control of GnRH)
- Lactoroph cells - Release PRL Prolactin (governed by inhibitory factors eg dopamine)
FSH
Stimulates follicular development in females (maturation of immature Graafian follicles).
Enhances production of androgen-binding protein by Sertoli cells in males and is crucial for spermatogenesis.
LH
Triggers follicular maturation, ovulation and CL (corpus luteum) formation in females (luteinisation)àHigh amplitude pre-ovulatory LH release is responsible for ovulation and luteinisation, with basal pulsatile LH secretion occurring between these pre-ovulatory surges.
In males, LH stimulates testosterone production in Leydig cells of the testes (increased plasma LH – increased testosterone synthesis & secretion). Testosterone is secreted after small LH pulses, which occur every 2-6 hours.
Pineal Gland
Pineal gland
• Environmental (e.g. seasonal) factors, as well as hormonal factors, are responsible for reproductive activity
• Melatoninergic cells (pinealocytes) release melatonin in response to light stimuli (photoperiods), which acts as a hormone and influences seasonality of reproduction