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Lecture 14

Lecture 14 - Mar 13.doc

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PSYC 342
Jens C Pruessner

PSYC342 Lecture 14 - Mar. 13 Female Menstrual Cycle: Stage 1: Post-menstrual late-follicular stage (Days 10-12 after onset of menses): High estrogen levels through the develop- • ing follicles • Stage 2: Pre-menstrual late-luteal stage (Days 1-5 before the onset of menses): Low estrogen levels - after ovulation break- down of corpus luteum - was more dominant in proges- terone production anyhow FSH + LH levels rise at the end of the menstrual period. • These rising levels of FSH will causes ovarian follicles to start growing • Primary follicles produce and release estrogen - As estrogen levels in- creases, they will feedback negatively on the pituitary and hypothalamus, thereby lowering GnRH, FSH, and LH levels Eventually one follicle will become dominant • • Near the end of the follicular phase, the level of FSH is low, due to inhibition exerted by estrogen • As a result of this scarcity in FSH, only the follicle with the most FSH receptors expressed can acquire enough FSH to con- tinue growing The other follicles eventually atrophy • Mechanisms of Menopause: • Menopause is defined as ‘pause of the menses’ - an absence of menses > 12 months • Not the same as amenorrhea - absence of menses in a women of reproductive age • Termination of ovulation means termination of menstrual cycle • Preceded by ‘Perimenopause’ - up to six years before menopause irregular menstrual cycles • At birth, a human female has between three and seven million follicles • At begin of puberty, that number is significantly lower (1/10 to 1/30) • At onset of menopause, the count is down to < 0.1% of the original number LH/FSH will fail to induce follicle growth • • Without follicle growth, no estrogen release to inhibit LH/FSH • LH/FSH levels remain high • Estrogen levels remain low • Progesterone levels remain low • No follicle development/dominance/ovulation • Menstruation stops, cycling stops, chances for subsequent menstrual cycle fur- ther reduced • Hormone levels fluctuate, causing disturbances similar to adolescence Mean age of menopause is 51 (range [±2 SD] is 45-57) • • Onset before age 45 is considered premature menopause • Younger age of natural menopause is generally linked with several adverse health outcomes, including • Cardiovascular disease • Osteoporosis • Overall mortality • Late menopause carries a higher risk of breast and endometrial cancer Hormone Replacement Therapy: After onset of menopause, substitution of estrogen and progesterone • • Will not induce ovulation • Will not induce menstrual cycle • However, will cure side effects of hormonal imbalance • Will have the effects that estrogen normally has • What effects of estrogen in the CNS are the desirable ones to consider HRT? Estrogen Receptor Location: • Estrogen receptors are located within the hippocampus (HC), especially the CA1 region, but also in the CA3 region and dendate gyrus (DG) Estrogen & Estrogen Receptors: • Estrogen Like all steroid hormones, can diffuse across the cell membrane to activate receptors • • Estrogen receptors • DNA binding transcription factor that regulates gene expression • Estrogen effect could act • Directly on hippocampal pyramidal cells • On connections between hippocampal regions • On support cells surrounding the neuronal cells i.e. Astrocytes (a type of glial cell) NMDA Receptors: • Estrogen may induce an increase in NMDA receptor binding in the hippocampus • Activating NMDA receptors via glutamate induces new excitatory synapses to develop • Blocking NMDA receptors prevents estrogen-induced synaptogenesis (formation of new synapses) Inhibitory GABA I
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