Modulation of hepatic adrenergic receptor ontogeny by thyroid hormone.
During hepatic development, beta-adrenergic receptors are replaced by alpha 1-receptors, an important event in the switchover from neonatal to adult glucose metabolism. In mature tissues, expression of adrenergic receptor subtypes is regulated, in part, by thyroid hormones; the current study examines whether they also participate in the transition of hepatic receptors. When triiodothyronine (T3) was given to rat pups on postnatal days 11-15, just before the receptor transition period, the developmental increase of alpha 1-receptors was accelerated but there was no change in the ontogenetic decline of beta-receptors. When propylthiouracil (PTU) was given over the same period to induce hypothyroidism, neither alpha 1- nor beta-receptor development were affected, thus, despite the selective promotion of alpha 1-receptor sites by exogenous thyroid hormone, endogenous hormone is not obligatory for receptor switching to take place. Finally, to distinguish whether the receptor transition is a function of general growth and cell differentiation, which are also impacted by thyroid status, animals were given PTU from gestational day 17 through postnatal day 5, a treatment that reproduces the growth defects of congenital cretinism, but that allows hormone levels to return to normal during the receptor transition period; the appropriate switchover still occurred. These studies indicate that thyroid hormone selectively promotes hepatic alpha 1-receptor expression during development, but is not itself responsible for the ontogenetic switchover in adrenergic receptor subtypes. Because other factors, such as glucocorticoids, have similar modulatory effects, the timing of hepatic adrenergic receptor development may be governed by multiple factors, no one of which is absolutely sufficient or essential.
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- Triiodothyronine
- Thyroid Hormones
- Receptors, Adrenergic, beta
- Receptors, Adrenergic, alpha-1
- Receptors, Adrenergic
- Rats, Sprague-Dawley
- Rats
- Propylthiouracil
- Pregnancy
- Pharmacology & Pharmacy
Citation
Published In
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Triiodothyronine
- Thyroid Hormones
- Receptors, Adrenergic, beta
- Receptors, Adrenergic, alpha-1
- Receptors, Adrenergic
- Rats, Sprague-Dawley
- Rats
- Propylthiouracil
- Pregnancy
- Pharmacology & Pharmacy