beta-endorphin and Hypothyroidism

The purpose of this study is to assess the effects of hypothyroidism on the hypothalamic-pituitary-adrenal (HPA) axis; the functional integrity of each component of the HPA axis was examined in short-term and long-term hypothyroidism. Neuropeptide synthesis, release, and content were evaluated in vitro both in the hypothalamus and anterior pituitary, and corticosterone release was assessed in primary adrenal cell cultures at 7 (short-term) and 60 days (long-term hypothyroidism) after thyroidectomy in male rats. Hypothyroid rats showed adrenal insufficiency in several parameters, which were associated with the duration of hypothyroidism. Cerebrospinal (CSF) ACTH was decreased in all hypothyroid animals, while CSF corticosterone levels were significantly decreased only in long-term hypothyroidism. Long-term hypothyroid animals showed decreased corticotropin-releasing hormone (CRH) mRNA expression in the hypothalamic paraventricular nucleus under both basal and stress conditions, decreased CRH release from hypothalamic organ cultures after KCL and arginine vasopressin stimulation, as well as an increased number of anterior pituitary CRH receptors. In contrast, short-term hypothyroid rats showed changes in anterior pituitary function with an increased responsiveness to CRH that was associated with an increase in CRH receptors. Although both short- and long-term hypothyroidism was associated with significant decreases in adrenal weights, only long-term hypothyroid rats showed changes in adrenal function with a significant decrease of ACTH-induced corticosterone release from cultured adrenal cells. The data suggest that long-term hypothyroidism is associated with adrenal insufficiency with abnormalities in all three components of the HPA axis. Short-term hypothyroidism, on the other hand, is associated with increased pituitary corticotroph responsiveness to CRH.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; beta-Endorphin; Corticosterone; Hypertonic Solutions; Hypothalamo-Hypophyseal System; Hypothyroidism; In Situ Hybridization; Male; Organ Culture Techniques; Organ Size; Pituitary-Adrenal System; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; Receptors, Corticotropin-Releasing Hormone; Thymus Gland; Thyroid Function Tests; Thyroid Hormones; Thyroidectomy

The aim of the present study was to evaluate the time-dependent effect of an experimentally induced hypothyroid state on prolactin (PRL) secretion in rats. Treatment with radioactive iodine and propylthiouracil (PTU) resulted in reduced serum concentrations of total thyroxine and triiodothyronine, and increased serum TSH concentrations in rats one week after the start of the treatment. Basal serum PRL concentrations were not significantly altered in 1-, 2- and 4-week hypothyroid rats, whereas in 8-week hypothyroid rats, serum PRL concentrations were significantly reduced and remained depressed throughout 24 weeks of PTU ingestion. The PRL response to i.p. administration of haloperidol (0.5mg/kg) was significantly reduced after one week of PTU ingestion. When the duration of hypothyroidism was increased, there was a progressive fall in the PRL response to haloperidol that reached the lowest value after 12 weeks of PTU ingestion. The PRL response to an i.v. bolus injection of vasoactive intestinal peptide (VIP, 150 mu g/kg) was markedly reduced in hypothyroid rats after one week of PTU ingestion and reached the lowest value after two weeks. The PRL response to VIP was progressively recovered after treatment for 4 weeks with PTU, and reached the highest value in 24-week hypothyroid rats. However, the PRL response to VIP in 24-week hypothyroid rats was significantly lower than that in euthyroid rats. Serum PRL response to an i.v. bolus injection of beta -endorphin (450 mu g/kg) was significantly reduced in 8-week hypothyroid rats. Dopamine (DA) concentrations in the pituitary and the hypothalamus were not significantly altered in 2-week hypothyroid rats. In contrast, DA concentrations were significantly increased in both the pituitary and hypothalamus in 8- and 24-week hypothyroid rats. These findings observed in hypothyroid rats were reversed by the administration of thyroxine and triiodothyronine for 9 days. The present results support a modulatory role for thyroid status in regulating the concentration of DA in the pituitary and the hypothalamus, and consequently on PRL secretion by the pituitary. This suggests that PRL releasing factors do not appear to play a major role in PRL secretion in hypothyroid rats. These data also indicate that alterations in PRL secretion and DA concentrations in the pituitary and the hypothalamus in the hypothyroid state become more prominent as the duration of hypothyroidism increases.

Topics: Animals; beta-Endorphin; Dopamine; Haloperidol; Hypothalamus; Hypothyroidism; Male; Pituitary Gland; Prolactin; Rats; Rats, Wistar; Time Factors; Vasoactive Intestinal Peptide

A comparison of the effect of PTU-induced hypothyroidism on the contents of immunoactive met-enkephalin and beta-endorphin in the pituitaries from rats aged 2 1/2, 12, and 18 months was made. In all ages, there was significant reduction of IR-met-enkephalin content in the anterior lobe and IR-beta-endorphin content in the neuro-intermediate lobe after PTU treatment. There was a significant age-related decrease in IR-beta-endorphin content in the anterior lobe. Rats of all three ages responded to PTU treatment with an increase in serum TSH level and a drastic reduction in serum T3 and T4 levels. The results indicate that there was no age-related difference in the change of pituitary opioid peptide contents in response to hypothyroidism.

Topics: Aging; Animals; beta-Endorphin; Enkephalin, Methionine; Hypothyroidism; Male; Pituitary Gland; Rats; Thyrotropin; Thyroxine; Triiodothyronine

The changes in met-enkephalin and beta-endorphin contents in the pituitary in PTU-induced hypothyroidism were studied in the rat. After 2 weeks of PTU-treatment, both IR-met-enkephalin and IR-beta-endorphin contents in the pituitary were significantly reduced. Gel filtration chromatography followed by radioimmunoassay showed that the immunoactivities in the peaks of precursors, met-enkephalin, beta-lipotropin and beta-endorphin were all lower in the pituitaries from the PTU-treated rats. In another experiment, some of the PTU-treated rats were injected daily with 500 micrograms T3/kg b.w. In the hypothyroid rats, IR-met-enkephalin and IR-beta-endorphin contents were decreased in both the anterior and neurointermediate lobes. Only the changes in the anterior lobe were reversed by T3 treatment. In conclusion, while the effects on the anterior lobe are probably due to a deficiency in thyroid hormones, the mechanism for the decrease of opioid peptide contents in the neurointermediate lobe is still unclear.

Topics: Animals; beta-Endorphin; Enkephalin, Methionine; Hypothyroidism; Kinetics; Male; Pituitary Gland; Pituitary Gland, Anterior; Pituitary Gland, Posterior; Propylthiouracil; Rats; Rats, Inbred Strains; Triiodothyronine