Background
Fetal programming
The process by which an organism grows and develops is critical to the future of the individual, affecting its survivability and its success to procreate. Two factors affecting the developmental process are the organisms’ genetics, and the environment in which this development occurs. Most vertebrates are sensitive to environmental stress, which allows them to take altered developmental trajectories in an attempt to reach a suitable phenotype for that new environment. This sensitivity may sometimes have adverse effects that resonate into maturity and possibly into following generations. In humans chronic diseases such as cardiovascular disease and diabetes have been associated with low birth weight due to reduced maternal nutrition. Environmental factors that affect development include, but are not restricted to, incubation temperature, foetal nutrition, and the availability of oxygen.
Cardiac β-Adrenergic receptors and hypoxia
β-Adrenergic receptors regulate inotropy (contractility) and chronotropy (rate) of the heart and are essential for its normal function. These receptors are stimulated by hormones called catecholamines in the circulation. During a hypoxic challenge the release of these hormones into the circulatory system is increases, subsequently increasing the stimulation of β-Adrenergic receptors. Over stimulation of β-Adrenergic receptors triggers physiological changes in the heart. Chronic prenatal hypoxia increases the sensitivity of beta adrenergic receptors in the broiler chicken embryo, with no significant effect on the density of the receptors. Later on in life the β-Adrenergic receptors of these prenatally hypoxic chickens show decreased sensitivity to catecholamine stimulation, again with no change in receptor density.
Hypothesis
The β2-Adrenergic receptor, a subtype of β-Adrenergic receptors, is capable of binding to both inhibitory and stimulatory Gα proteins, which are essential in the transduction of the signal from the β-Adrenergic receptors to effectors which mediate the above mentioned physiological responses to stimulation. Changes in the levels of expression of these Gα proteins could alter the sensitivity of the β-Adrenergic receptors, as an increase in stimulatory Gα protein would increase stimulation i.e. sensitivity, and an increase in inhibitory Gα protein would cause a decrease in stimulation. If hypoxia alters the levels of expression of Gα proteins in the heart, this may explain the changes observed in the sensitivity of cardiac β-Adrenergic receptors in chickens developing in chronic hypoxia.
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Last updated:
05/18/10