Endo part 1.pdf

• Lecture 11: Neuroendocrine Control I • The brain-pituitary-gonadal axis • Stress – adrenal axis • C144/244 • F. Gomez-Pinilla, IBP, UCLA c144/244; F. Gomez-Pinilla, UCLA Hypothalamus-pituitary- gland axis c144/244; F. Gomez-Pinilla, UCLA c144/244; F. Gomez-Pinilla, UCLA c144/244; F. Gomez-...

• Lecture 11: Neuroendocrine Control I • The brain-pituitary-gonadal axis • Stress – adrenal axis • C144/244 • F. Gomez-Pinilla, IBP, UCLA c144/244; F. Gomez-Pinilla, UCLA Hypothalamus-pituitary- gland axis c144/244; F. Gomez-Pinilla, UCLA c144/244; F. Gomez-Pinilla, UCLA c144/244; F. Gomez-Pinilla, UCLA Hypothalamus-pituitary-gonad axis • Gonadotropin releasing hormone (GnRH) produced by hypothalamic neurons stimulate production of gonadotropins from ant. pituitary gonadotropes: • Luteinizing hormone (LH) • Follicle-stimulating hormone (FSH) • Activity of the axis varies during lifespan c144/244; F. Gomez-Pinilla, UCLA Hypogonadal (hpg) mice is an animal model to study the Kallmann’s Syndrome - genetic defect in GnRH production, but gonadal function can be restored in both sexes with pusatile GnRH. c144/244; F. Gomez-Pinilla, UCLA c144/244; F. Gomez-Pinilla, UCLA c144/244; F. Gomez-Pinilla, UCLA c144/244; F. Gomez-Pinilla, UCLA Circadian control of reproduction • • • • Season is main factor in controlling reproduction in most mammal Day length determines melatonin production Melatonin production controls seasonal reproduction ablation of SCN disrupts estrus cycle by affecting release of GnRH from hypoth/pituitary • Melatonin affects the function and size of gonads c144/244; F. Gomez-Pinilla, UCLA Photoperiodicity regulates melatonin synthesis c144/244; F. Gomez-Pinilla, UCLA Pulsatile stimulation of pituitary gonadotropes is crucial to maintain normal LH/FSH secretion: • Exposure of pituitary to continuous GnRH leads to downregulation of GnRH receptors • Importance of a physiological frequency of GnRH pulses that varies across age and circumstances • narrow window of acceptable frequencies to stimulate GnRH without downregulation c144/244; F. Gomez-Pinilla, UCLA c144/244; F. Gomez-Pinilla, UCLA Feedback control of GnRH release • Hypothalamic level; feedback regulation decreases pulse frequency of GnRH and LH • Effects can be direct on GnRH neurons or indirect via brain regions that project onto GnRH neurons using (GABA, catecholamines) or endorphins (opiates). • Pituitary, Feedback (-) by estradiol and testosterone decrease LH pulses by reducing sensitivity to GnRH • Inhibin is a glycoprotein produced by gonads that acts at the pituitary to suppress FSH release • Ovarectomy (OVX) decreases synaptic input on GnRH neurons c144/244; F. Gomez-Pinilla, UCLA Factors causing alterations in ovarian function • Menopause: depletion of ovarian follicles -- loss of estrogen production releases feedback (-) on hypoth (high LH/FSH). Tissue damage (osteoporosis, cardiovascular disease) • Circadian, diurnal rhythms - testosterone (night), LH (day) • Environmental polymodal hypothalamic input, such as: • Seasonal, environmental adaptation signaled by day length • Nutritional factors, undernutrition can disrupt ovarian cycle or spermatogenesis. • Extraneous exercise can disrupt ovarian cycle • Chronic stress acting at hypothalamic and pituitary levels can suppress pulsatile release of GnRH and LH c144/244; F. Gomez-Pinilla, UCLA •STRESS: Adaptive response to noxious stimuli, e.g., disease, fever, psychological