Nitric oxide synthase-containing cells were visualized in the anterior pituitary gland by immunocytochemistry. Consequently, we began an evaluation of the possible role of NO in the control of anterior pituitary function.Prolactin is normally under inhibitory hypothalamic control, and in vitro the gland secretes large quantities of the hormone. When hemipituitaries were incubated for 30 min in the presence of sodium nitroprusside, a releaser of NO, prolactin release was inhibited. This suppression was completely blocked by the scavenger of NO, hemoglobin. Analogs of arginine, such as NG-monomethyl-L-arginine (NMMA, where NG is the terminal guanidino nitrogen) and nitroarginine methyl ester, inhibit NO synthase. Incubation of hemipituitaries with either of these compounds significantly increased prolactin release. Since in other tissues most of the actions of NO are mediated by activation of soluble guanylate cyclase with the formation of cyclic GMP, we evaluated the effects of cyclic GMP on prolactin release. Cyclic GMP (10 mM) produced an "40%o reduction in prolactin release. Prolactin release in vivo and in vitro can be stimulated by several peptides, which include vasoactive intestinal polypeptide and substance P. Consequently, we evaluated the possible role of NO in these stimulations by incubating the glands in the presence of either of these peptides alone or in combination with NMMA. In the case of vasoactive intestinal polypeptide, the significant stimulation of prolactin release was augmented by NMMA to give an additive effect. In the case of substance P, there was a smaller but significant release of prolactin that was not significantly augmented by NMMA. We conclude that NO has little effect on the stimulatory action of these two peptides on prolactin release. Dopamine (0.1 ,uM), an inhibitor of prolactin release, reduced prolactin release, and this inhibitory action was significantly blocked by either hemoglobin (20 jig/ml) or NMMA and was completely blocked by 1 mM nitroarginine methyl ester. Atrial natriuretic factor at 1 ,uM also reduced prolactin release, and its action was completely blocked by NMMA. In contrast to these results with prolactin, luteinizing hormone (LH) was measured in the same medium in which the effect of nitroprusside was tested on prolactin release, there was no effect of nitroprusside, hemoglobin, or the combination of nitroprusside and hemoglobin on luteinizing hormone release. Therefore, in contrast to its inhibitory action on prolactin release NO had no effect on luteinizing hormone release. Immunocytochemical studies by others have shown that NO synthase is present in the folliculostellate cells and also the gonadotrophs of the pituitary gland. We conclude that NO produced by either of these cell types may diffuse to the lactotropes, where it can inhibit prolactin release. NO appears to play little role in the The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accorda...
To examine the role of thyroid parasympathetic innervation in organ's function, rats subjected to inferior laryngeal nerve (ILN) section were employed. This procedure decreased thyroid [3H]choline uptake by about half. Bilaterally ILN-sectioned rats treated with methylmercaptoimidazole for 4 days exhibited a significant impairment of the methylmercaptoimidazole-induced goitrogenic response. Unilateral ILN section resulted in further atrophy of the ipsilateral thyroid lobe in hypophysectomized rats. One week after ILN section a significant decrease of serum T4 and an increase of serum TSH were observed. Bilateral ILN section generally decreased circulating T4 for up to 28 days after surgery, while a unilateral ILN section caused a transient T4 decrease for 1 week after surgery. Compensatory thyroid growth in rats subjected to unilateral thyroidectomy (hemi Tx) and ILN section performed ipsilaterally to the remaining lobe, was significantly smaller than that of rats subjected to hemi Tx alone. Hemi Tx depressed serum T4 and increased serum TSH levels significantly. These hormonal changes were prevented by unilateral superior cervical ganglionectomy (SCGx), but were unaffected by ILN section. The combination of SCGx and ILN section negated the facilitating effect of SCGx on thyroid secretion and impaired the increase in compensatory thyroid growth brought about by thyroid sympathetic denervation. Thyroid mitotic index studies in hemi Tx rats receiving ILN section, SCGx, or a combination of both indicated that the increase in the number of follicular mitosis caused by hemi Tx was significantly impaired by ILN section and was significantly increased by SCGx. SCGx potentiation of thyroid follicular mitotic activity was partially prevented by concomitant ILN section. These results support a significant role of thyroid sympathetic and parasympathetic innervation in the control of organ's growth and secretory activity.
The functional and anatomic compensatory response of the parathyroid gland was examined in hemiparathyroidectomized (HPTx) rats whose parathyroid hormone (PTH) secretion was stimulated by a low calcium diet. These responses were compared with those observed in the thyroid gland of hemithyroidectomized (HTx) rats. Rats kept on a low calcium diet for 10 days were subjected to HPTx, HTx, or sham operations. Throughout the experiment (up to 28 days after surgery), serum calcium levels of HPTx rats were lower than the basal, with delta values (mg/dl, mean +/- SEM) of -0.66 +/- 0.17 and -0.84 +/- 0.17, (P less than 0.05) 3 and 28 days after surgery, respectively. Serum PTH decreased significantly from 7 to 21 days after HPTx, reaching normality at day 28 after surgery. In HTx rats, serum thyroxine (T4) levels diminished significantly 7 days after surgery, and attained normality thereafter. The mitotic index (number of metaphases/1,000 cells) in parathyroid glands of colchicine-treated HPTx rats increased significantly in comparison to sham-operated controls, when examined 2 or 40 days after surgery. The mitotic index of thyroid follicular cells was significantly higher than that of their respective controls, 2 but not 40 days after HTx. These results indicate that after HPTx, a delayed compensatory response is found when the animals are kept under a low calcium diet. Parathyroid response is both delayed and of a minor degree compared to that found in the thyroid gland after HTx.
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