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I. Overview: the Hypothalamic/pituitary/ovarian/endometrial Axis
A. One of four principal endocrine systems (aside from glucose Ca++ control)
B. Not necessary for survival C. Primary roles
1. Reproduction
2. Maintenance of estrogen-dependent tissues
3. Growth and development
II. The Hypothalamic Gonadotropin-releasing Hormone Pulse Generator abnormal periods
A. Located in the arcuate nucleus
B. Receives multiple inputs
1. Dopaminergic
2. Noradrenergic
3. Opioidergic
4. Possibly "cortical"
5. Possibly "metabolic"
C. Gonadotropin-releasing hormone (GnRH) pulses released at "basal" rate of 1 pulse/hour
D. Transport to anterior pituitary via portal blood system
III. The Anterior Pituitary
A. Site of pulsatile gonadotropin secretion in response to GnRH
B. Up-regulation vs down-regulation
C. The luteinizing hormone I4) surge
1. Possible mechanisms
2. Mystery of positive feedback
D. Modulators of pulse frequency: the progesterone/endorphin axis
IV. The Ovary
A. The two-cell theory of ovarian steroidogenesis
1. LH interacts with theca cells and yields androgen production
2. Follicle-stimulating hormone (FSH) interacts with granulosa cells and yields aromatization of androgens to estrogens
3. Is LH really necessary in the follicular phase?
B. Ovulation
C. Luteinization of the follicle leads to progesterone production; is FSH really
necessary in the luteal phase?
D. Local (paracrine) control mechanisms
1. Insulin-like growth factor-1
2. Inhibin: an endocrine/paracrine hybrid
3. Others
a. Epidermal growth factor
b. Transforming growth factor-a
c. Fibroblast growth factor
d. Platelet-derived growth factor
e. Angiogenic growth factors
V. The Endometrium
A. Only physiologic role is to support implantation
B. Estrogen serves to stimulate endometrial proliferation
C. Progesterone inhibits estrogen-induced proliferation and induces