Functional and morphological characteristics of transplantable rat pituitary tumors established in nude mice

Two strains of transplantable rat pituitary tumors, MtT SA5 and MtT SA6, have been established in female nude mice from a single original pituitary tumor which had spontaneously occurred in a female Wistar rat at 759 days of age. MtT SA5 tumor produces prolactin (PRL), growth hormone, and adrenocorticotropic hormone, and MtT SA6 tumor secretes PRL and growth hormone. Additionally, both tumors induce severe nephropathy and promote pathogenicity of murine hepatitis virus, resulting in hepatic necrosis. Electron micrographs of MtT SA5 and MtT SA6 tumors revealed three and two types of cells, respectively, in reference to secretory granules. The tumors seem to consist of mixed population, each cell secreting each hormone. Since marked adrenal enlargement and relatively low serum corticosterone levels were found in MtT SA5-bearing rats, it is suggested that MtT SA5 tumor secretes adrenocorticotropic hormone and/or its related peptides which induce adrenal hyperplasia with little or no stimulation of corticoid production. In nude mice bearing MtT SA5 tumor, concentrations of growth hormone in serum and tumor tissue were exceedingly higher than those of PRL, while they were in the same magnitude in MtT SA6-bearing nude mice. We also found that PRL levels in serum and tumor tissue of MtT SA5-bearing nude mice were much higher in males than females, although those of MtT SA5-bearing rats were not significantly different in both sexes.     

Stimulatory effects of retinoic acid on tumor growth and serum insulin-like growth factor-1 in rats bearing estrogen-responsive pituitary tumor MtT/Se

MtT/Se is one of 4 cell lines derived from an estrogen-dependent pituitary tumor, MtT/F84. The main difference between these tumor types is that MtT/F84 secretes both growth hormone (GH) and prolactin (PRL) whereas MtT/Se secretes only GH. MtT/Se grew slowly in ovariectomized (ovex) rats, but tumor growth was much faster in estrogen-treated ovex rats. Effects of dietary retinoic acid (RA) on tumor growth, serum GH and insulin-like growth factor-1 (IGF-1) levels were examined in ovex rats. Latency of tumor growth was shortened, and tumor take and weight were promoted by all-trans RA both in the presence and absence of exogenous estrogen. Serum GH and IGF-1 levels became increased in tumor-bearing rats whereas PRL levels remained unchanged. Serum IGF-1 levels exhibited a good correlation with tumor weights (r = 0.84). Our results suggest a close relationship between increase of tumor weight and stimulation of serum IGF-1 level by RA in tumor-bearing rats.     

Stimulatory Effects of Retinoic Acid on Tumor Growth and Serum Insulin-like Growth Factor-1 in Rats Bearing Estrogen-responsive Pituitary Tumor MtT/Se

MtT/Se is one of 4 cell lines derived from an estrogen-dependent pituitary tumor, MtT/F84. The main difference between these tumor types is that MtT/F84 secretes both growth hormone (GH) and prolactin (PRL) whereas MtT/Se secretes only GH. MtT/Se grew slowly in ovariectomized (ovex) rats, but tumor growth was much faster in estrogen-treated ovex rats. Effects of dietary retinoic acid (RA) on tumor growth, serum GH and insulin-like growth factor-1 (IGF-1) levels were examined in ovex rats. Latency of tumor growth was shortened, and tumor take and weight were promoted by all- trans RA both in the presence and absence of exogenous estrogen. Serum GH and IGF-1 levels became increased in tumor-hearing rats whereas PRL levels remained unchanged. Serum IGF-1 levels exhibited a good correlation with tumor weights ( r =0.84). Our results suggest a close relationship between increase of tumor weight and stimulation of serum IGF-1 level by RA in tumor-bearing rats.     

Estrogen Receptor Levels and Tumor Growth in a Series of Pituitary Clonal Cell Lines in Rats

Four kinds of in vitro clonal pituitary tumor cell lines named MtT/Se, MtT/SM, MtT/S and MtT/ E, each of which shows different sensitivity to estrogen on proliferation, were inoculated into fat pad of ovariectomized rats and estrogen-loaded ovariectomized rats at 10⁵ and 10⁶ cells/site. They formed tumor with average latency ranging from 30 to 71 in ovariectomized rats and 13 to 63 days in estrogenized rats inoculated with 106 cells. MtT/Se was highly sensitive to estrogen for growth, and MtT/SM also grew well in estrogenized rats. With MtT/S and MtT/E, there was no significant shortening of average tumor latency in estrogenized rats. In vivo , the cytosolic estrogen receptor (ER) levels of MtT/Se, SM, S and E were measured to be 452 ±66, 370 ±115, 260 ±16 and 83 ±8 fmol/ mg protein, respectively. In vitro , however, the lowest ER level was noted in MtT/Se. Histologically, all four tumors grown in rats were composed of homogeneous round cells, and MtT/Se contained particularly large nucleated cells. In MtT/E, the cells appeared to be changing into ftbromatous cells. Three cell lines except MtT/E maintained the function of hormonal secretion in vivo as well as in vitro . Serum GH level was increased in rats with MtT/Se and MtT/S. Increased levels of both prolactin and growth hormone were measured in sera of rats with MtT/SM. Increases of hormones as well as tumor sizes were promoted by the estrogen.     

Estrogen receptor levels and tumor growth in a series of pituitary clonal cell lines in rats.

Four kinds of in vitro clonal pituitary tumor cell lines named MtT/Se, MtT/SM, MtT/S and MtT/E, each of which shows different sensitivity to estrogen on proliferation, were inoculated into fat pad of ovariectomized rats and estrogen-loaded ovariectomized rats at 10(5) and 10(6) cells/site. They formed tumor with average latency ranging from 30 to 71 in ovariectomized rats and 13 to 63 days in estrogenized rats inoculated with 10(6) cells. MtT/Se was highly sensitive to estrogen for growth, and MtT/SM also grew well in estrogenized rats. With MtT/S and MtT/E, there was no significant shortening of average tumor latency in estrogenized rats. In vivo, the cytosolic estrogen receptor (ER) levels of MtT/Se, SM, S and E were measured to be 452 +/- 66, 370 +/- 115, 260 +/- 16 and 83 +/- 8 fmol/mg protein, respectively. In vitro, however, the lowest ER level was noted in MtT/Se. Histologically, all four tumors grown in rats were composed of homogeneous round cells, and MtT/Se contained particularly large nucleated cells. In MtT/E, the cells appeared to be changing into fibromatous cells. Three cell lines except MtT/E maintained the function of hormonal secretion in vivo as well as in vitro. Serum GH level was increased in rats with MtT/Se and MtT/S. Increased levels of both prolactin and growth hormone were measured in sera of rats with MtT/SM. Increases of hormones as well as tumor sizes were promoted by the estrogen.     

Hormones of the pituitary-adrenal axis in rats bearing the Walker 256 carcinoma

Male Sprague-Dawley rats (125-150 g) were implanted intramuscularly with the Walker 256 carcinoma. After 3, 5 or 7 days, tumor-bearing rats, along with controls, were killed and plasma levels of adrenocorticotropic hormone (ACTH), beta-endorphin and corticosterone were assessed. Plasma levels of all 3 hormones declined with time following tumor implantation. Plasma levels of ACTH and corticosterone were statistically significantly less than plasma levels of these same hormones in control rats by 7 days post-implantation. Levels of these hormones were reduced by 42% and 33%, respectively, relative to control levels by 7 days. beta-Endorphin levels declined much more rapidly following tumor implantation than did either of the other 2 hormones. beta-Endorphin was significantly decreased by 3 days post-implantation and by 7 days the plasma levels of this factor were 83% lower than in control rats.     

Mammotropic and somatotropic hormones in sera of normal rats and in rats bearing primary and grafted pituitary tumors

Parallel determinations were made of the concentration of MtH and StH in the sera of rats with spontaneous, estrogen-induced and grafted pituitary tumors and, for a base, in sera of normal rats of both sexes, in various physiologic states, following oophorectomy and treatment with gonadal hormones. The characteristic sharp rise of MtH during proestrus was confirmed. This was not accompanied by a rise in StH. Following oophorectomy the levels of both hormones dropped. After estrogen treatment of normal rats, both hormones rose gradually, reaching very high levels with development of pituitary tumors. Similar increases were found with spontaneous mammotropic tumors (MtH) in rats of both sexes. Seven MtT's, originating in six different strains, were studied in the course of successive transplantations. All exhibited mammary gland stimulation, with very high MtH and StH levels, depending on the tumor size and tumor strain. In general, hormone secretion decreased in the course of successive transplantations. One variant of the originally typical MtT.W5, MtT.W5/H, markedly lost the ability to produce MtH while maintaining the ability to produce StH, as indicated by both radioimmunoassays and biological changes in the tumor hosts. The oldest transplantable tumor of this series (MtT.F4), secreted large quantities of AtH and StH without biological evidence of somatotropic effects. The StH effect became “unmasked” by adrenalectomy. Biological evidence of AtH secretion by the other MtH strains was inconstant and variable. It was often present in the first transplant generation but vanished in the course of successive transplantations with the exception of the F4 strain. The MtH values in normal as well as MtT-bearing hosts were higher in female than in male rats. There was relatively more StH in males than in females.     

Analysis of prolactin and growth hormone production in hyperplastic and neoplastic rat pituitary tissues by the hemolytic plaque assay

The reverse hemolytic plaque assay (RHPA) was used to detect hormone release from cultured normal, hyperplastic, and neoplastic rat pituitary cells. Hyperplastic pituitary cells were produced by s.c. diethylstilbestrol (DES) treatment (10 mg in Silastic tubes) for 3, 6, and 9 weeks. Neoplastic pituitary cells from rats with MtT/W15 transplantable tumors treated with DES for 3 weeks were also analyzed. Aliquots of the same cells were also analyzed by immunocytochemical staining. DES treatment resulted in an increase in prolactin (PRL)-producing cells in hyperplastic pituitaries compared to untreated pituitaries after 9 weeks of treatment by the RHPA [61.2 +/- 5.2 (SE) versus 32 +/- 3.0] and by immunocytochemical staining [70.9 +/- 2.4 versus 36 +/- 1.4]. The percentage of mammosomatotropic cells decreased from 11.3 +/- 3.8 to 4.2 +/- 2.6% in pituitary cells from these same groups of animals. After 3 weeks of DES treatment in rats with MtT/W15 tumor, there was an increase in growth hormone (GH)-producing cells and a decrease in PRL-producing cells when analyzed by the RHPA (control: percentage of GH, 36.3 +/- 6.2; percentage of PRL, 39.0 +/- 1.6 versus DES-treated tumors: percentage of GH of 68.2 +/- 1.9; and percentage of PRL, 3.2 +/- 1.8%). The percentage of mammosomatotropic cells declined from 12.4 +/- 2.3 to 0.77 +/- 2.4%. A combined procedure of RHPA followed by immunocytochemical staining on the same slides also revealed a decline in mammosomatotropic cells after chronic DES treatment in hyperplastic and neoplastic MtT/W15 tumor cells. These results show that DES has different effects on PRL and GH secretion and storage in hyperplastic pituitary and in the MtT/W15 pituitary tumor cells.     

Inhibition of Mammary Tumors by Pretreatment with 17β-Estradiol in F344 Rats Induced with N-Methyl-N-nitrosourea

The influence of 17β-estradiol (E2) and prolactin was studied on N-methyl-N-nitrosourea (MNU)-induced mammary carcinomas (MCAs) in rats. MNU was intravenously injected once into seven-week-old female F344 rats at a dose of 50 mg/kg body weight. Groups of rats also received either 2.5 mg of E2 or a continuous supply of prolactin and/or growth hormone via transplanted MtT/F84 (mammo-somatotropic pituitary tumor). Rats were observed for up to 36 weeks after MNU administration. Although simultaneous administration of MNU and E2 did not much affect the occurrence of MCAs as compared to administration of MNU alone, rats treated with 2.5 mg of E2 for two weeks before MNU administration had significantly reduced occurrence of MCAs compared to those given MNU alone. In contrast, rats with MNU plus MtT/F84 showed high incidence and shortened latency of MCAs and they also had a high incidence of clitorial gland hyperplasias. Average pituitary weights and serum prolactin levels in E2-treated rats were greatly increased compared to those of MNU-alone rats. Average serum E2 levels were about 100 ng/ml in E2-treated rats and 0.05 ng/ml in rats without E2 treatment. Serum prolactin levels were greatly increased in rats with MtT/F84. The results indicated that pretreatment with E2 before MNU administration was inhibitory while increased prolactin caused by grafting MtT/F84 after MNU injection was promotive for the occurrence of MCAs in female F344 rats.     

Pituitary hormones and the metabolism of N-hydroxy-N-2-fluorenylacetamide in female rats

The transplantable functional pituitary tumor, Furth MtT/F4, enhances hepatoma formation by the carcinogen N-hydroxy-N-2-fluorenylacetamide (N-OH-FAA) in rats. Therefore the metabolism of a single intraperitoneal dose of N-OH-FAA-9-¹⁴C was followed in groups of female Fischer rats which were fed either N-OH-FAA-containing or control diets for 8 weeks, with or without MtT implantation. The MtT markedly increased rectal temperature, food and water intake, urinary volume and body, liver, and kidney weights. The carcinogen-prefeeding alone did not affect the total percentage of radioactivity from labeled N-OH-FAA excreted in 24-hour urine, but the proportion excreted as urinary glucosiduronic acids and as the glucuronide of N-OH-FAA was greater. MtT implantation had no significant effect on the urinary metabolites in the animals on a control diet. However, the combination of carcinogen-prefeeding and MtT transplantation increased the urinary excretion of total radioactivity, the urinary glucosiduronic acids, and especially the glucuronide of N-OH-FAA. Maintenance of higher levels of N-OH-FAA, the altered endocrine situation and the increased metabolic rate may contribute to the enhancement of hepatoma formation in female rats implanted with MtT.     

Effects of estradiol on prolactin and growth hormone messenger RNAs in cultured normal and neoplastic (MtT/W15 and GH3) rat pituitary cells

The effects of 17 beta-estradiol (E17 beta) on prolactin (PRL) cell proliferation and on the expression of PRL and growth hormone (GH) proteins and mRNAs were analyzed in cultured pituitary cells by immunocytochemistry, in situ hybridization, and Northern blot hybridization studies. Three different cell cultures were used: (a) normal pituitary cells; (b) GH3 tumor cell line; and (c) MtT/W15, a transplantable PRL and GH-producing pituitary tumor. E17 beta (10(-7) M) caused a significant increase in PRL cell proliferation in normal pituitary [3.9 +/- 0.4 versus 7.7 +/- 0.9% (SEM) of immunostained PRL cells with thymidine incorporation] [P less than 0.01] but produced a significant decrease in PRL cell proliferation in MtT/W15 primary cell cultures [6.7 +/- 1.0 versus 3.7 +/- 0.8%] [P less than 0.05]. PRL mRNA was significantly increased in normal pituitary and in GH3 tumor cells by E17 beta treatment. There was a significant decrease in PRL mRNA and an increase in GH mRNA expression in cultured MtT/W15 tumor cells by immunocytochemistry and in situ hybridization analyses. The percentage of cells producing both PRL and GH or mammosomatotropic cells analyzed by two different techniques declined after one week in culture in normal pituitary cells and in cultured MtT/W15 tumor cells after E17 beta treatment. These results show that E17 beta has a direct stimulatory effect on normal pituitary and GH3 cells and a direct inhibitory effect on MtT/W15 tumor cells with respect to cell proliferation and PRL hormone and mRNA expression.     

Effect of 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis on the opioid peptide levels in the rat central nervous system

Mammary tumors were induced in female Sprague-Dawley rats by giving a single oral dose of 20 mg 7,12-dimethylbenz[a]anthracene (DMBA). Animals were killed after full development of tumors 4 months after the ingestion of DMBA. Opioid peptides in various tissues were estimated by radioimmunoassay (RIA). Tumor-bearing rats (n = 5) had higher (P less than 0.05) contents of beta-endorphin in pituitary (+60%), striatum (+52%) and midbrain (+85%) compared to animals with no tumors. However, tumor-bearing rats showed a decrease of 35% in striatal met-enkephalin content. Dynorphin level decreased (P less than 0.05) in pituitary (-49%) and hypothalamus (-29%) of tumor-bearing rats. Thus for the first time, we report the alteration in the level of these neuropeptides during the process of chemical carcinogenesis.     

Growth-promoting effect of retinoic acid in transplantable pituitary tumor of rat

MtT/F84 grew well in Fischer rats (F344), but tumor growth was promoted in hyperestrogenized rats. Effects of dietary retinoic acid (RA) on tumor growth, estrogen receptor (ER) and serum growth hormone (GH) level were examined. Tumor latency became shortened, and tumor take and weight were promoted by all-trans RA at dosages of 50 and 200 mg/kg basal diet, but not dose-dependently. ER level was elevated in tumor of RA-treated rats, whereas the retinoic acid-binding protein level remained unchanged. RA also elevated incorporation of 5-bromo-2'-deoxyuridine, a thymidine analogue, into DNA of tumor cells. Average serum GH level was increased in tumor-bearing rats treated with RA and was well correlated with tumor weight. RA may directly affect ER level and enhance estrogenic action, resulting in promotion of tumor growth, or it may act independently for tumor growth and elevation of serum GH level.     

Stereotactic radiosurgery for patients with ACTH-producing pituitary adenomas after prior adrenalectomy

PURPOSE: To review the results of stereotactic radiosurgery for patients with adrenocorticotropic hormone (ACTH)-producing pituitary adenomas after bilateral adrenalectomy. METHODS AND MATERIALS: Eleven patients with ACTH-producing pituitary adenomas after bilateral adrenalectomy underwent radiosurgery between 1990 and 1999. Nine patients had documented tumor growth, hyperpigmentation, and elevated ACTH levels (median 920 ng/mL) at the time of radiosurgery. Five of these patients had tumor enlargement despite prior fractionated radiotherapy (median dose 50 Gy). Two patients were treated prophylactically within 1 month of their adrenalectomies to prevent future tumor growth. The median follow-up was 37 months (range 22-74). RESULTS: Tumor growth control was achieved in 9 patients (82%); 2 patients had had continued tumor growth after radiosurgery. The ACTH levels decreased a median of 66% (range -99% to +27%); 4 patients had normal ACTH levels. Three patients had radiation-related complications, including diplopia (n = 2), ipsilateral blindness (n = 1), testosterone/growth hormone deficiency (n = 1), and asymptomatic temporal lobe radiation necrosis (n = 1): all had received prior radiotherapy. One patient who had undergone three prior resections and radiotherapy died 59 months after radiosurgery despite two additional attempts at tumor resection. CONCLUSION: Although our experience is limited, it appears that radiosurgery provides tumor control for most patients with ACTH-producing pituitary adenomas who have undergone bilateral adrenalectomy.     

Multiple hormone receptors in the adenylate cyclase of human adrenocortical tumors

Adenylate cyclase responses to pituitary hormones including adrenocorticotropic hormone (ACTH), biogenetic amines, prostaglandin E1 (PGE1), angiotensin II, and glucagon were evaluated in adrenocortical tumors and hyperplastic adrenal tissues, obtained from patients with Cushing's syndrome at surgery, and in normal adrenals. The adenylate cyclase of two normal adrenals was activated only by ACTH and PGE1 among the hormones tested, while that of two hyperplastic adrenal tissues due to excessive pituitary ACTH secretion was stimulated only by ACTH. Of five ACTH-responsive adrenocortical adenomas, in contrast, three were stimulated by norepinephrine, two by epinephrine, one by thyroid-stimulating hormone, and one by luteinizing hormone in addition to ACTH, indicating the presence of multiple receptors for hormones other than ACTH and PGE1 in these four tumors. The cyclase of an ACTH-unresponsive adrenocortical carcinoma ws activated only by PGE1 and not by other hormones including ACTH, whereas that of an ACTH-responsive adrenocortical nodular hyperplasia was stimulated by ACTH and glucagon but not by other hormones including PGE1. These results indicate the presence of multiple receptors for hormones other than ACTH and PGE1, the normal adrenocortical stimulants, in human adrenocortical tumors, particularly in adrenal adenomas, but not in normal and hyperplastic (of whichever an etiology) adrenocortical tissues, suggesting a functional alteration of the cellular membrane receptors in human adrenocortical tumors.     

The conversion of an ovariectomy-nonresponsive to an ovariectomy-responsive mammary tumor strain.

MTW9, a transplantable mammary tumor in Wistar Furth rats, shows little growth unless host serum prolactin is increased. This study compares the response to ovariectomy of MTW9-MtT, a tumor developed in rats bearing the mammosomatotropic tumor MtTW10 (serum prolactin 500 to 7000 ng/ml) with MTW9-P developed in rats given chronic perphenazine treatment (4 mg/kg/day). Serum prolactin concentrations were 150 to 600 ng/ml in MTW9-P bearing rats. MTW9-MtT does not regress after ovariectomy but does regress after surgical removal (resection) of MtT. Ovariectomy plus MtT resection leads to greater tumor regression than MtT resection alone. MTW9-P does not regress when perphenazine administration is stopped but does regress after ovariectomy, whether or not rats are given perphenazine. Administration of estradiol (10 mug/day) to rats with complete ovariectomy-induced regression of MTW9-P results in regrowth of tumor. These data suggest that MTW9-P may represent a clone of MTW9 with a lower requirement for prolactin.     

Growth-promoting Effect of Retinoic Acid in Transplantable Pituitary Tumor of Rat

MtT/F84 grew well in Fischer rats (F344), but tumor growth was promoted in hyperestrogenized rats. Effects of dietary retinoic acid (RA) on tumor growth, estrogen receptor (ER) and serum growth hormone (GH) level were examined. Tumor latency became shortened, and tumor take and weight were promoted by all- trans RA at dosages of 50 and 200 mg/kg basal diet, but not dose-dependently. ER level was elevated in tumor of RA-treated rats, whereas the retinoic acid-binding protein level remained unchanged. RA also elevated incorporation of 5-bromo-2'-deoxyuridine, a thymidine analogue, into DNA of tumor cells. Average serum GH level was increased in tumor-bearing rats treated with RA and was well correlated with tumor weight. RA may directly affect ER level and enhance estrogenic action, resulting in promotion of tumor growth, or it may act independently for tumor growth and elevation of serum GH level.     

Differential expression of galectin-3 in pituitary tumors

Galectin-3 (Gal-3), a beta-galactoside-binding protein, has been implicated in a variety of biological functions, including cell proliferation and differentiation, tumor cell adhesion, angiogenesis, apoptosis, tumor progression, and metastasis. We investigated the role of Gal-3 in the development and progression of pituitary tumors. Immunohistochemical and Western blot analysis of normal and neoplastic human pituitaries showed that only lactotroph (PRL) and corticotroph (ACTH) hormone-producing cells and tumors expressed Gal-3. Gal-3 was present in 24 of 38 (63.2%) PRL adenomas, 5 of 6 (83.3%) PRL carcinomas, 19 of 41 (46.3) ACTH adenomas, and 7 of 8 (87.5%) ACTH carcinomas, but not in 112 other pituitary adenomas and carcinomas. Pituitary folliculo-stellate cells, which have macrophage-type functions in the anterior pituitary, also expressed Gal-3. Hyperplastic and neoplastic pituitaries from p27(Kip1) (p27)-null mice, which produce mainly ACTH, showed increased Gal-3 expression levels compared with control mice. Treatment with transforming growth factor beta1, which regulates pituitary cell proliferation, reduced Gal-3 as well as p27 expression levels in cultured HP75 pituitary cells and Gal-3 in cultured pituitary cells from p27-null mice, suggesting that p27 is not necessary for the inhibitory effects of transforming growth factor beta1 on the cell cycle in the pituitary. The role of Gal-3 in pituitary cell function was examined by RNA interference experiments. Inhibition of Gal-3 gene expression by RNA interference decreased HP75 cell proliferation and increased apoptosis. These results indicate that Gal-3 has an important role in pituitary cell proliferation and tumor progression.     

ghrelin和生长抑素在光动力学疗法治疗肿瘤中的作用

目的：研究光动力学疗法对动物肿瘤生长的影响及生长抑素（somatostantin，SS）、ghrelin表达的变化。方法：选用皮下接种W256瘤细胞株制成实验性荷瘤大鼠，观察经紫外光照射、充氧并加注血卟啉的血液对大鼠移植肿瘤生长的影响，同时采用放射免疫检测方法观察血浆、组织中SS含量的改变；采用实时PCR和免疫荧光组化方法观察了ghrelinm RNA和ghrelin在脑内表达的影响。结果：荷瘤大鼠输入经紫外光照射、充氧并加注血卟啉的血液，其肿瘤生长速度明显减慢，肿瘤重量明显减轻（P〈0．01）。荷瘤大鼠下丘脑、中脑、桥延脑、肝脏、瘤组织及血浆SS含量与正常大鼠比较显著增加（P〈0．05），下丘脑、垂体ghrelin mRNA表达显著减少，同时下丘脑弓状核（Are）内ghrelin免疫阳性细胞显著减少（P〈0．01），但经光动力学疗法治疗肿瘤后，上述各组织和血浆中SS含量明显下降（P〈0．01），下丘脑、垂体ghrelin mRNA含量和下丘脑弓状核内ghrelin免疫阳性细胞数量均显著增加（P〈0．05）。结论：光动力学疗法对肿瘤生长有抑制作用；肿瘤生长过程中激活某种途径刺激机体产生生长抑素以提高机体抵抗肿瘤生长的能力，同时ghrelin也参与了肿瘤的发生和发展。     

Promoting action of prolactin released from a grafted transplantable pituitary tumor (MtT/F84) on rat prostate carcinogenesis

The potential modifying effects of high prolactinemia on rat prostate carcinogenesis was investigated. Male F344 rats were treated at 5 times of 5-week intervals with s.c. injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB), each injection following 3 weeks pretreatment with dietary ethinyl estradiol. After completion of the carcinogen administration stage, rats received multiple s.c. transplantations of a prolactin producing transplantable pituitary tumor, MtT/F84 until sacrifice at week 51. The effects of additional or single treatment with bromocriptine, a prolactin suppressing agent, were also investigated. The body, liver and kidney but prostate weights were significantly increased in the groups given MtT/F84. Although the development of prostate carcinomas was not affected by the observed hyperprolactinemia, the incidences of atypical hyperplasia of both ventral and lateral prostate were significantly enhanced. The findings thus indicate that prolactin may have promoting potential for prostate carcinogenesis.