George N. Wade

Bio: George N. Wade is an academic researcher from University of Massachusetts Amherst. The author has contributed to research in topics: Estradiol benzoate & Estrous cycle. The author has an hindex of 48, co-authored 132 publications receiving 8433 citations. Previous affiliations of George N. Wade include University of Rochester & Monell Chemical Senses Center.

Control of fertility by metabolic cues

Abstract: In female mammals, reproduction is extremely sensitive to the availability of oxidizable metabolic fuels. When food intake is limited or when an inordinate fraction of the available energy is diverted to other uses such as exercise or fattening, reproductive attempts are suspended in favor of processes necessary for individual survival. Both reproductive physiology and sexual behaviors are influenced by food availability. Nutritional effects on reproductive physiology are mediated by changes in the activity of gonadotropin-releasing hormone (GnRH) neurons in the forebrain, whereas the suppression of sexual behaviors appears to be due, at least in part, to decreases in estrogen receptor in the ventromedial hypothalamus. Work using pharmacological inhibitors of glucose and fatty acid oxidation indicates that reproductive physiology and behavior respond to short-term (minute-to-minute or hour-to-hour) changes in metabolic fuel oxidation, rather than to any aspect of body size or composition (e.g., body fat content or fat-to-lean ratio). These metabolic cues seem to be detected in the viscera (most likely in the liver) and in the caudal hindbrain (probably in the area postrema). This metabolic information is then transmitted to the GnRH-secreting or estradiol-binding effector neurons in the forebrain. There is no evidence to date for direct detection of metabolic cues by these forebrain effector neurons. This metabolic fuels hypothesis is consistent with a large body of evidence and seems to account for the infertility that is seen in a number of situations, including famine, eating disorders, excessive exercise, cold exposure, lactation, some types of obesity, and poorly controlled diabetes mellitus.

Some effects of ovarian hormones on food intake and body weight in female rats.

Abstract: Ovarian steroids affect the food intake and body weight of rats. These effects are probably mediated by estradiol and progesterone, since these 2 hormones are more effective than their principal metabolites (estrone and 5alpha-pregnane-3,20-dione, respectively) in altering the food intake and body weight of ovariectomized rats. Estradiol seems to affect food intake by lowering the set point about which body weight is regulated in a dose-dependent fashion. These actions of estradiol can be attenuated or completely blocked by concurrent injections of progesterone. Estradiol-treated ovariectomized rats are far more responsive to the weight- and appetite-promoting actions of progesterone than are ovariectomized-adrenalectomized rats, suggesting that the principal action of progesterone on energy balance may be to interfere with the effects of estradiol.

Human biochemical genetics

Abstract: So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Brown Adipose Tissue: Function and Physiological Significance

Abstract: Cannon, Barbara, and Jan Nedergaard. Brown Adipose Tissue: Function and Physiological Significance. Physiol Rev 84: 277–359, 2004; 10.1152/physrev.00015.2003.—The function of brown adipose tissue i...

Prolactin: Structure, Function, and Regulation of Secretion

Abstract: Prolactin is a protein hormone of the anterior pituitary gland that was originally named for its ability to promote lactation in response to the suckling stimulus of hungry young mammals. We now know that prolactin is not as simple as originally described. Indeed, chemically, prolactin appears in a multiplicity of posttranslational forms ranging from size variants to chemical modifications such as phosphorylation or glycosylation. It is not only synthesized in the pituitary gland, as originally described, but also within the central nervous system, the immune system, the uterus and its associated tissues of conception, and even the mammary gland itself. Moreover, its biological actions are not limited solely to reproduction because it has been shown to control a variety of behaviors and even play a role in homeostasis. Prolactin-releasing stimuli not only include the nursing stimulus, but light, audition, olfaction, and stress can serve a stimulatory role. Finally, although it is well known that dopamine of hypothalamic origin provides inhibitory control over the secretion of prolactin, other factors within the brain, pituitary gland, and peripheral organs have been shown to inhibit or stimulate prolactin secretion as well. It is the purpose of this review to provide a comprehensive survey of our current understanding of prolactin's function and its regulation and to expose some of the controversies still existing.

Profound Peripheral Insulin Resistance, Independent of Obesity, in Polycystic Ovary Syndrome

Abstract: Hyperinsulinemia secondary to a poorly characterized disorder of insulin action is a feature of the polycystic ovary syndrome (PCO). However, controversy exists as to whether insulin resistance results from PCO or the obesity that is frequently associated with it. Thus, we determined in vivo insulin action on peripheral glucose utilization (M) and hepatic glucose production (HGP) with the euglycemic glucose-clamp technique in obese ( n = 19) and nonobese ( n = 10) PCO women and age- and body-composition-matched normal ovulatory women ( n = 11 obese and n = 8 nonobese women). None had fasting hyperglycemia. Two obese PCO women had diabetes mellitus, established with an oral glucose tolerance test; no other women had impairment of glucose tolerance. However, the obese PCO women had significantly increased fasting and 2-h glucose levels after an oral glucose load and increased basal HGP compared with their body-composition-matched control group. There were statistically significant interactions between obesity and PCO in fasting glucose levels and basal HGP ( P < .05). Steady-state insulin levels of ∼100 μU/ml were achieved during the clamp. Insulin-stimulated glucose utilization was significantly decreased in both PCO groups whether expressed per kilogram total weight ( P < .001) or per kilogram fat free mass ( P < .001) or when divided by the steady-state plasma insulin (I) level (M/I, P < .001). There was residual HGP in 4 of 15 obese PCO, 0 of 11 obese normal, 2 of 10 nonobese PCO, and 0 of 8 nonobese normal women. The metabolic clearance rate of insulin did not differ in the four groups. We conclude that 1 ) PCO women have significant insulin resistance that is independent of obesity, changes in body composition, and impairment of glucose tolerance, 2 ) PCO and obesity have a synergistic deleterious effect on glucose tolerance, 3 ) hyperinsulinemia in PCO is not the result of decreased insulin clearance, and 4 ) PCO is associated with a unique disorder of insulin action.

Sexual differentiation of the central nervous system

Abstract: Sexual differentiation of reproductive and behavior patterns is largely effected by hormones produced by the gonads. In many higher vertebrates, an integral part of this process is the induction of permanent and essentially irreversible sex differences in central nervous function, in response to gonadal hormones secreted early in development.