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Reproduction is enormously costly in energetic terms, and
female mammals, including women, will defer reproduction by
ceasing to ovulate when the food supply is limited or when
other physiological processes (e.g., exercise or
thermoregulation) require excessive amounts of energy.
Examples of nutritional infertility in humans include the
amenorrhea and infertility that are seen in women with
eating disorders or in endurance athletes (e.g., distance
runners).
We have used a number of approaches to study the effects
of nutrition on reproductive physiology and behaviors in
laboratory rodents, including treatment with pharmacological
agents that selectively inhibit glucose or fatty acid
utilization, experimental diabetes mellitus and insulin
treatment, and manipulations of energy expenditure via
changes in exercise and ambient temperature.
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Nutritional Infertility, Hormones and Energy
Balance
This work reveals that both reproductive physiology
(secretion of GnRH and gonadotropins) and behaviors (sexual
receptivity and maternal behavior) are sensitive to
minute-to-minute changes in the availability of metabolic
fuels, and not to any aspect of body size or composition
(fat content), as previously supposed.
Metabolic fuel availability is detected by cells in the
caudal hindbrain and is then relayed to neurons in the
forebrain, which control reproductive behaviors.
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Nutritional manipulations which inhibit sexual behavior also
alter levels of estrogen and progestin receptors in these
neural loci, suggesting that altered binding of gonadal
steroids contributes to the behavioral changes.
Thus, we have some idea as to: a) The nature of the
relevant metabolic cues - short-term changes in metabolic
fuel oxidation. b) The sites where these signals are
detected - the caudal hindbrain. c) The effector pathways -
forebrain circuits controlling reproductive behaviors.
Our current research focuses on the on the neural
pathways by which nutritional information is transmitted
from the hindbrain fuel detectors to the forebrain effector
neurons that control reproductive function. Neuropeptides
which affect the regulation of energy balance, such as
neuropeptide Y and corticotropin-releasing hormone, seem to
play an important role in this regard. We continue to
investigate which other neurotransmitter systems play a role
in nutritional infertility as well as how and where they
interact.
For additional information,
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Working hypothesis as to how metabolic fuel
information is detected and transmitted to forebrain circuits which
control reproductive behaviors. Metabolic fuel detectors appear to
reside in the caudal hindbrain, perhaps in the area postrema (AP).
This information is then relayed synaptically to the forebrain
circuits which regulate reproductive behaviors (blue arrows). Ongoing
work indicates that neuropeptides, such as neuropeptide Y and
corticotropin-releasing hormone, play a significant role in this
process. Our work provides no evidence whatsoever for the possibility
that metabolic fuel availability might be detected by forebrain
effector neurons (orange arrow).
Selected Papers on Nutritional Infertility:
Publications
with links to Medline Pub Med and Acrobat Reader
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- Schneider, JE, and GN Wade. 1989. Availability of metabolic
fuels controls estrous cyclicity of Syrian hamsters.
Science 244: 1326-1328. Subsequent exchange of letters with
Rose Frisch.
Pub
Med:
Wade, GN, JE Schneider, and MI Friedman. 1991.
Insulin-induced anestrus in Syrian hamsters. American Journal of
Physiology 260: R148-R152.
Wade, GN, and JE Schneider. 1992. Metabolic fuels and reproduction
in female mammals. Neuroscience and Biobehavioral Reviews
16: 235-272.
Berriman, SJ, GN Wade, and JD Blaustein. 1992. Expression of
Fos-like proteins in gonadotropin-releasing hormone neurons of
Syrian hamsters: Effects of estrous cycles and metabolic fuels.
Endocrinology 131: 2222-2228.
Dickerman, RW, H-Y Li, and GN Wade. 1993. Decreased
availability of metabolic fuels suppresses estrous behavior in Syrian
hamsters. American Journal of Physiology 264:
R568-R572.
Schneider, JE, DG Friedenson, AJ Hall, & GN Wade. 1993.
Glucoprivation induces anestrus and lipoprivation may induce
hibernation in Syrian hamsters. American Journal of Physiology
264: R573-R577.
Li, H-Y, GN Wade, and JD Blaustein. 1994. Manipulations of
metabolic fuel availability alter estrous behavior and neural
estrogen-receptor immunoreactivity in Syrian hamsters.
Endocrinology 135: 240-247, 1994.
Wade, GN, JE Schneider, and H-Y Li. 1996. Invited review: Control
of fertility by metabolic cues. American Journal of Physiology
270: E1-E19. Subsequent exchange of letters with R.E. Frisch.
Du, Y, GN Wade, and JD Blaustein. 1996. Effects of food
deprivation on induction of neural progestin receptors by estradiol
in Syrian hamsters. American Journal of Physiology 270:
R978-R983.
Wade, GN, RL Lempicki, AK Panicker, RM Frisbee, and JD Blaustein.
1997. Leptin facilitates and inhibits sexual behavior in female
hamsters. American Journal of Physiology 272: R1354-R1358.
Panicker, A.K. and G.N. Wade. (1998). Insulin-induced
repartitioning of metabolic fuels inhibits estrous behavior in Syrian
hamsters: Role of area postrema. American Journal of
Physiology 274: R1094-R1098.
Wade, G.N. (1998). Energy balance: Effects on reproduction. In:
Encyclopedia of Reproduction, (E. Knobil & J.D. Neill, editors),
San Diego: Academic Press, 1091-1100.
Panicker, AK, RA Mangels, JB Powers, GN Wade, and JE Schneider.
1998. AP lesions block suppression of estrous behavior, but not
estrous cyclicity, in food-deprived Syrian hamsters. American
Journal of Physiology 275: R158-R164.
Early, AH, GN Wade, and RL Lempicki. 1999. Effects of cold
exposure on estrous behavior and neural estrogen receptor in Syrian
hamsters. Physiology & Behavior 65: 763-768, 1999.
Schneider, JE, RM Blum, and GN Wade. 2000. Metabolic control of
food intake and estrous cycles in Syrian hamsters. I. Plasma insulin
and leptin. American Journal of Physiology, 278:
R476-R480.
Corp, ES, B Gréco, JB Powers, CL Marìn Bivens, and
GN Wade. 2001. Neuropeptide Y inhibits estrous behavior and
stimulates food intake through separate receptors in Syrian hamsters.
American Journal of Physiology, 280: R1061-R1068.
Jones, JE, and LS Lubbers. 2001. Suppression and recovery of
estrous behavior in Syrian hamsters following changes in metabolic
fuel availability, American Journal of Physiology, 280:
R1093-R1098.
Jones, JE, ES Corp, & GN Wade. 2001 Effects of
naltrexone and CCK on estrous behavior and food intake in Syrian
hamsters. Peptides, 22: 601-606.
URL:
http://www-unix.oit.umass.edu/~gwade/juli%20CCK%20naltrexone.pdf
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