role of vasoactive intestinal polypeptide (vip) in regulating pituitary function

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312 Role of Vasoactive Intestinal Polypeptide (VIP) in Re~ulatin~ Pituitary Function; YUZURU KATO, AKIRA SHIMATSU, NORIO MATSUSHITA, HIKARU OHTA and HIRO0 IMURA; (Second Medical Clinic, Department of Medicine, Kyoto University Faculty of Medicine, Kyoto, Japan) We have previously reported that VIP stimulates prolactin (PRL) secretion in rats, acting at least in part directly on the pituitary. VIP was highly concentrated in the hypophysial portal blood and raised by serotonin which is known to stimulate PRL secretion, suggesting a possible role of rIP as PRF in PRL secretion in the rat. In the clinical studies, intramuscular injection of synthetic VIP (200 ~g) resulted in a 4- to 7-fold increase in plasma PRL levels in normal women, which was accompanied by a 553±56% (mean±SE) increase in peripheral plasma VIP levels at 15 min after the injection. Plasma growth hormone (GH) and cortisol levels were not changed by VIP. The injection of VIP raised plasma PRL in some patients with hyperprolactinemia and plasma GH in some patients with acromegaly. In an in vitro superfusion system, VIP stimulated PRL release in a dose- related manner from dispersed PRL producing pituitary tumor cells, and GH release from pituitary adenoma cells obtained from acromegalic patients. VIP concentrations in the cerebrospinal fluid were elevated in some patients with hyperprolactinemia and acromegaly. These findings suggest that VIP plays some role in regulating PRL secretion in man as well as in rats and may affect GH secretion from pituitary adenoma in acromegaly. Vipergic innervation in diabetic pancreas of rats S. KISHIMOTO, G. KAJIYAMA, A. MIYOSHI, N. YANAIHARA (Department of Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minamiku, Hiroshima 734 Japan The changes of VIPergic innervations were studied ~Tmunocytoch~mically in diabetic pancreas of rats. (Method) Diabetes was produced in rats by injectionof streptozoto- cin (80mg/kg). The rats were sacrificed 6 months after the treatment. Insulin and blood sugar levels in blood taken were determined for the diagnosis of diabetes. Three micron-wax pancreas tissue fixed in Bouin's solution was stained with HE for histopat~logy. Ten.micron frozen tissue fi.~edin p-benz_oquinone was reacted withanti serum of VIP(I :100) for VIP nerves by indirect immunofluorescence. The absorption test was done for the specificity of VIP identified. Rats injected with saline were used as the control. (Results) The B-cells were atrophied and reduced in hyperglyce- mic (350+10,c:120+21mg/dl) and hypoinsulinemic(38+10,c:120+21)/U~ml) rats. Both e~Dc- rine and endocrine pancreas were l~ly replaced by fibrous tissue and cell-infiltr- ation, resulting in marked reduction of islets,parench3~nal cells and nerve gan~lions. Conozlmitently VIP nerves were also diminished to innervate e2~xzrine and endocrine pancreas. Decreased eMocrine function was confirmed by P-S test. At the levels of ~M, survived ganglionic cells were degenerated. Reduced and diminished VIPergie innervation as well as reduction of nerve ganglions may play one of major roles in not only endocrine but e~crine dysfunction of diabe- tic pancreas in the rat induced by streptozotocin.

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312

Role of Vasoactive Intestinal Polypeptide (VIP) in Re~ulatin~ Pituitary Function; YUZURU KATO, AKIRA SHIMATSU, NORIO MATSUSHITA, HIKARU OHTA and HIRO0 IMURA; (Second Medical Clinic, Department of Medicine, Kyoto University Faculty of Medicine, Kyoto, Japan)

We have previously reported that VIP stimulates prolactin (PRL) secretion in rats, acting at least in part directly on the pituitary. VIP was highly concentrated in the hypophysial portal blood and raised by serotonin which is known to stimulate PRL secretion, suggesting a possible role of rIP as PRF in PRL secretion in the rat.

In the clinical studies, intramuscular injection of synthetic VIP (200 ~g) resulted in a 4- to 7-fold increase in plasma PRL levels in normal women, which was accompanied by a 553±56% (mean±SE) increase in peripheral plasma VIP levels at 15 min after the injection. Plasma growth hormone (GH) and cortisol levels were not changed by VIP.

The injection of VIP raised plasma PRL in some patients with hyperprolactinemia and plasma GH in some patients with acromegaly. In an in vitro superfusion system, VIP stimulated PRL release in a dose- related manner from dispersed PRL producing pituitary tumor cells, and GH release from pituitary adenoma cells obtained from acromegalic patients. VIP concentrations in the cerebrospinal fluid were elevated in some patients with hyperprolactinemia and acromegaly.

These findings suggest that VIP plays some role in regulating PRL secretion in man as well as in rats and may affect GH secretion from pituitary adenoma in acromegaly.

Vipergic innervation in diabetic pancreas of rats S. KISHIMOTO, G. KAJIYAMA, A. MIYOSHI, N. YANAIHARA (Department of Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minamiku, Hiroshima 734 Japan

The changes of VIPergic innervations were studied ~Tmunocytoch~mically in diabetic pancreas of rats. (Method) Diabetes was produced in rats by injectionof streptozoto- cin (80mg/kg). The rats were sacrificed 6 months after the treatment. Insulin and blood sugar levels in blood taken were determined for the diagnosis of diabetes. Three micron-wax pancreas tissue fixed in Bouin's solution was stained with HE for histopat~logy. Ten.micron frozen tissue fi.~edin p-benz _oquinone was reacted withanti serum of VIP(I :100) for VIP nerves by indirect immunofluorescence. The absorption test was done for the specificity of VIP identified. Rats injected with saline were used as the control. (Results) The B-cells were atrophied and reduced in hyperglyce- mic (350+10,c:120+21mg/dl) and hypoinsulinemic(38+10,c:120+21)/U~ml) rats. Both e~Dc- rine and endocrine pancreas were l~ly replaced by fibrous tissue and cell-infiltr- ation, resulting in marked reduction of islets,parench3~nal cells and nerve gan~lions. Conozlmitently VIP nerves were also diminished to innervate e2~xzrine and endocrine pancreas. Decreased eMocrine function was confirmed by P-S test. At the levels of ~M, survived ganglionic cells were degenerated.

Reduced and diminished VIPergie innervation as well as reduction of nerve ganglions may play one of major roles in not only endocrine but e~crine dysfunction of diabe- tic pancreas in the rat induced by streptozotocin.