1. Neuroendocrine Control of Gonadotropin Secretion: Comparative Aspects
Chapter 33
Neuroendocrine Control of Gonadotropin Secretion: Comparative Aspects
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2. FIGURE 33.1 Patterns of follicular estradiol (E2: solid lines) and luteal progesterone (Prog: dashed lines) to illustrate ovarian cycles of women and other primates (panel A); domestic animals and guinea pigs (panel B); mice, rats, and hamsters (panel C); and reflex ovulators (panel D). Ovulation (ovary–ovum symbol) occurs on day 14 of the primate menstrual cycle and day 0 of the estrous cycle in other mammals. In most rodents, and all reflex ovulators, coitus (arrow) is needed to induce a full-length luteal phase. Also note that in some species (e.g., rodents and primates), the follicles also secrete progesterone, while in others (e.g., some primates, and rabbits) the corpus luteum also produces E2; these steroid patterns have been omitted from this figure in the interests of simplicity. Hormonal patterns taken for panels A–D are based on data in women,1 sheep,2 rats,3 and rabbits,4 respectively.
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3. FIGURE 33.2 Administration of the α-adrenergic receptor antagonist dibenamine (DiB) and the cholinergic receptor antagonist atropine (At), at or before 1400 h of proestrus, blocks ovulation in rats. If given at 1600 h or thereafter, these drugs have little or no effect on ovulation. M: midnight. Source: Data redrawn from Everett et al.29
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4. FIGURE 33.3 Effects of different neural de-afferentation procedures on ovulation in ovary-intact rats and serum LH in OVX rats. Panel A: schematic of Halasz knife that was lowered down between the two hemispheres to perform de-afferentations. By combining rotation of the knife 90° so the blade is parallel to the third ventricle and moving it in the anterior–posterior plane, the cuts in panel B were performed. Panel B: Illustration of three types of knife cuts on a parasagittal schematic of the rat hypothalamus. Complete cuts (CC) severed all connections to the mediobasal hypothalamus (MBH), while frontal cuts (FC) severed inputs from the preoptic area (POA) and posterior cuts (PC) severed inputs entering laterally and posteriorly. Effects of cuts on ovulation rate (panel C) and on tonic LH secretion (panel D), illustrated as mean (±SEM) serum LH concentrations in samples collected from OVX (shaded bars) and ovary-intact (striped bars) rats during the morning; Cnt: controls. Note that LH was measured using the ovarian ascorbic acid depletion bioassay. Serum from ovary-intact rats produced a slight (nonsignificant) increase in ascorbic acid content of the ovaries, which is plotted as a negative value. Panels A, B, and C taken from a review by Haslaz35; panel D is based on data presented in Halasz and Gorski.36 AP: anterior pituitary; ca: anterior commissure; OCh: optic chiasm.
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5. FIGURE 33.4 LH pulse patterns on four different days of the menstrual cycle (left) and from two postmenopausal women (right). Note that y-axes on the right have been adjusted to start at 50 mIU/ml so that pulse amplitudes can be directly compared with those on the left. Source: Redrawn from Yen et al.88 with permission from the Endocrine Society.
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6. FIGURE 33.5 Effects of short-term and chronic treatment with E2 on the pituitary response to GnRH (plotted as mean ± SEM ΔLH) in rats,131 sheep,129,132 monkeys,128,133 and humans.134,135 With short-term treatments of E2, an initial (acute) suppression in response to GnRH is followed by stimulation of the response (prolonged treatment); in these panels, the nadir and peak responses are presented (see the text for approximate times of each). Chronic treatments with E2 were for 48 h in rats,131 7 days in sheep132 and women,135 and 13 days in rhesus monkeys.133 Data from sheep and short-term treatments in monkeys were collected using a hypophysial clamp approach; all other data were from animals or patients with an intact hypophysial–pituitary unit. Note that in most cases, data for short-term and chronic effects of E2 are from different studies and cannot be directly compared.
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7. FIGURE 33.6 Negative feedback actions of E2 on GnRH secretion measured in hypophysial portal blood in sheep,186 and push–pull perfusions of the median eminence in rabbits,76 monkeys,187,188 and rats.189,190 Mean (±SE) LH (in peripheral samples) and GnRH concentrations and GnRH pulse amplitude and frequency in sheep, rabbits, and monkeys are shown, but GnRH pulse parameters are not available in rats. Variabilities in data from sheep (SED) are presented as the standard error of mean of difference among groups from analysis of variance. Data from two different studies (labeled a187 and b188) in rhesus monkeys are presented to illustrate variability in the effects of E2. Data from rats compare mean GnRH values at 1300 h from OVX and intact (“low E” on diestrus and “high E” on proestrus) animals (bars on left)189 and from OVX and OVX + E rats (bars on right).190 Note that for data in sheep, mean GnRH is pg/10 min, while GnRH pulse amplitude is pg/pulse. *P < 0.05 versus no E group.
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8. FIGURE 33.7 Endogenous preovulatory LH (in peripheral samples) and GnRH surges measured in hypophysial portal blood in sheep,2 and push–pull perfusions of the median eminence in rabbits,227 monkeys,228 and rats.189 Note that widths of plots have been adjusted to illustrate differences in the duration of LH and GnRH surges across species. Redrawn with permission from the Endocrine Society.
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9. FIGURE 33.8 Schematic of parasagittal section of the hypothalamo– hypophysial unit illustrating the anatomical areas and neural systems participating in the preovulatory GnRH surge and sites of E2 positive feedback in various species. This figure is reproduced in color in the color plate section. All structures are required in rabbits; in other species, solid lines depict knife cuts that had no effect on the surge. Dotted lines are cuts that only decreased the amplitude of the LH surge, and the dashed line illustrates that NE input is normally required for the surge in rats but can be compensated for under some circumstances. See the text for more details. AP: anterior pituitary; GP: guinea pig; MB: mammillary body; OCh: optic chiasm; Pr: primate; Sh: sheep.
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10. FIGURE 33.9 Effects of coitus (arrow) on mean (±SEM) concentrations of norepinephrine (NE; solid symbols and lines) and GnRH (open symbols and dashed line) measured in push–pull perfusions collected every 2.5 min from the rabbit median eminence (n = 6). Data averaged from plots of individual animals.227 *First statistically significant increase in NE and GnRH over values before mating.
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11. FIGURE Schematic illustration of the time course of steroiddependent (solid lines) and steroid-independent (dashed lines) mechanisms inhibiting LH secretion before and through puberty in female and male rats, sheep, and rhesus monkeys and male hamsters. Time scale is in days for rats, weeks for hamsters and sheep, and months for primates. Men: menarche; Ov: first ovulation; Sp: first appearance of mature sperm in reproductive tract.
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12. FIGURE Schematic representation of systems inhibiting GnRH secretion (top panel) and the time course of FSH and LH concentrations (bottom panel) during lactation. In animals that do not have a postpartum ovulation, reproductive function is initially suppressed after parturition by lactation-independent effects of gestation (shaded bar). When the hypothalamus has recovered from the effects of gestation, GnRH secretion continues to be inhibited primarily by the effects of suckling, which may include both direct neural inhibition and the actions of elevated prolactin. As the offspring grow, the intensity of suckling decreases, but their metabolic demands increase so the latter becomes more important in suppressing GnRH secretion. In general, FSH returns to normal concentrations in the first half of lactation, so that episodic GnRH release and thus LH concentrations limit fertility. Weaning at any time after the postpartum period of infertility will result in a rapid increase in episodic GnRH secretion that soon results in ovulation.
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13. FIGURE Neural systems stimulating food intake and inhibiting GnRH secretion during lactation in the rat. This figure is reproduced in color in the color plate section. The suckling stimulus is transmitted to the hypothalamus via neurons in the lateral parabrachial nucleus (LPB) and ventrolateral medulla (VLM), inhibits DA release from tuberoinfundibular dopaminergic (TIDA) neurons and kisspeptin release from KNDy neurons, and stimulates NPY neural activity in the DMH. The fall in DA allows prolactin secretion to increase, which further inhibits KNDy kisspeptin and stimulates NPY from the DMH. The latter increases food intake, while the former inhibits GnRH secretion. At the same time, the negative energy balance in the mother induced by the demands of the offspring acts via the metabolic homeostatic circuitry in the ARC (increased NPY–AgRP and decreased POMC–CART), which also acts to stimulate food intake and may inhibit GnRH secretion. Note that this circuitry is depicted by a single neural element (NPY and POMC) for simplicity. Similarly, orexogenic neurons in the LHA and anorexogenic CRH neurons in the PVN are not illustrated.
© 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

14. FIGURE Schematic of parasagittal section of the hypothalamus illustrating mechanisms by which different external factors alter episodic GnRH secretion. This figure is reproduced in color in the color plate section. Note that neural inputs are conceptual and do not represent monosynaptic pathways. See the text for more details. Dep: steroid-dependent mechanisms; InD: steroid-independent mechanisms; Kiss: kisspeptin; NE: norepinephrine; Olf: olfactory epithelium; Un: unknown neurotransmitter.
© 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition