CHANGES OF SOMATOTROPES IN FEMALE RATS AFTER MULTIPLE AND CHRONICAL TREATMENT WITH SOMATOSTATIN

zoo· GH-immunoreactive cells of control adult female rat pituitaries were ovoid or pyramidal in shape, with a spherical centrally located nucleus. GH cells were usually situated along sinusoids. In SRIH-treated rats, these cells were smaller, irregularly shaped, with more intensely stained secretory granules. Blood capillaries were dilated. All morphometric parameters were decreased in both SRIH-treated groups comparing to saline-treated

GH-immunoreactive cells of control adult female rat pituitaries were ovoid or pyramidal in shape, with a spherical centrally located nucleus.GH cells were usually situated along sinusoids.In SRIH-treated rats, these cells were smaller, irregularly shaped, with more intensely stained secretory granules.Blood capillaries were dilated.All morphometric parameters were decreased in both SRIH-treated groups comparing to saline-treated The neuropeptide somatostatin (SRIH) originally isolated from the hypothalamus as a growth hormone (GH) release-inhibiting hormone, is widely distributed both in the central nervous system (R e i chi i n 1983) and in the peripheral tissues (S h u Ike s 1994).It is well known that SRIH inhibits GH release from somatotropes in male and female rats (M i los e vic et al.This study was designed to evaluate the effects of multiple and chronical sub cutaneous (s.c.) treatment with SRIH on the stereology and morphology of somatotropes in pituitary glands of the female rats.
The study was performed using adult female Wistar rats (210-230 g).The rats were divided into four experimental groups of five animals per group.The first group received two 100 fig/kg b.w.SRIH doses per day (R e b u f fat et al. 1984).for five consecutive days (75-79th day of life; multiple treatment).Females of the second group received two 20 Jlg/I00 g b.w.SRIH doses per day, from the 23rd day till the 71st day of life (chronical treatment).The somatostatin used was cyclic somatostatin-14 (Bachern, PSOMIO, USA).The third and the fourth group were the corresponding controls.Females of these groups were treated multiply or chronically with saline only.All animals were sacrificed under deep anesthesia by decapitation during 12 h after the last injection.Pituitary glands were excised, fixed in Bouin's solution and embedded in paraffin.Pituitary GH cells were immunocytochemically localized by the peroxidase-antiperoxidase-complex (PAP) method of S t ern b erg e r et al. (1970).Measurements were performed on the widest portion of the pituitary gland.Immunopositive GH cells were analyzed by the M42 test system after Wei bel (1979).For the calculations of the cell and nuclear volumes the formula of Wei bel (1979) was used.Morphometric data obtained from each group were averaged, and the standard deviation of the mean was calculated.A one-way analysis of variance (AN OVA), followed by the multiple range test of Duncan was used for statistical comparisons between the groups.A probability value of 5% or less was considered statistically significant.rats (Figs.1-3).The nuclear volume of GH cells was insignificantly decreased (p>o.05; by 15%) after both multiple and chronical SRIH-14 treatment in comparison with the corresponding controls (Fig. 1).111e cellular volume of GH cells was significantly decreased (p<0.05) in both multiply and chronically treated animals, by 39% and 56%, respectively (Fig 2), in relation to the corresponding controls.After chronical SRIH-14 treatment, the GH cells volume was lower by 22% (p<0.05)than after multiple SRIH-14 treatment.The volume density of GH cells in both SRIH-treated groups was decreased by 29% in the first and by 45% in the second group (p<0.05) in relation to the corresponding controls (Fig. 3).The volume density of GH cells in chronically treated rats was significantly decreased (p<o.05) by 28% in comparison with multiply SRIH-treated rats (Fig. 3).

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o Control previous observations that SRIH-14 and SRIH-28 given intracerebroventricularly to male and female rats led to a decrease in the number of GH cells, accompanied by a reduction in both their cellular and nuclear volumes in comparison with the controls (M i los e vic et aL 1998,2000).The inhibition of GH release by SRIH involves a change in the distribution of microfilaments rather than microtubules (S him a d a et aL 1990).These authors found microfilament bundles running parallel to the plasmalemma in the space between the granules after injection of SRIH.
In conclusion, systemic application of SRIH-14 by s.c.route induced marked changes in immunocytochemical and .morphometric characteristics of pituitary GH cells.The volume and volume density of GH cells were significantly reduced after multiple and chronical SRIH-14 treatment.However, in chronically treated females a more markedly expressed inhibitory effects of SRIH-14 on GH cells were found than in multiply treated animals.The results of the present study demonstrate that multiply or chronically applied SRIH-14 expressed an inhibitory influence on GH cells morphology in female rats.Morphometric and quantitative changes of GH pituitary cells were more obvious in animals chronically treated with SRIH-14 than after multiple SRIH-14 treatment.This data is in accordance with our
1998) via separate receptors in the plasma membrane ( W e h r e n b erg et al. 1982).Hypothalamic SRIH also inhibits secretion of luteinizing hormone (L 0 v r e n et al. 1998).prolactin (PRL) (M i los e vic • e t a I. 1998) and thyrotropin-stimulating hormone (TSH) (5 e k u lie et al. 2000; Milos e vic et al. 2000) from the anterior pituitary in rats.In many animal tumor models and cultured tumor cell lines, somatostatin and somatostatin analogs inhibit tumor growth (R e ubi and L a iss u e 1995), probably, because the highest incidence of somatostatin receptors was observed in neuroendocrine tumors (R e ubi 1997).