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PubMed2000

The influence of infiltrating lobular carcinoma on the outcome of patients treated with breast-conserving surgery and radiation therapy.

BACKGROUND: The role of conservative surgery and radiation therapy (CS and RT) in the treatment of patients with infiltrating ductal carcinoma is well established. However, the efficacy of CS and RT for patients with infiltrating lobular carcinoma is less well documented. The goal of this study was to examine treatment outcome after CS and RT for patients with infiltrating lobular carcinoma and to compare the results to those of patients with infiltrating ductal carcinoma and patients with mixed ductal-lobular histology. METHODS: Between 1970 and 1986, 1624 patients with Stage I or II invasive breast cancer were treated with CS and RT consisting of a complete gross excision of the tumor and > or = 6000 cGy to the primary site. Slides were available for review for 1337 of these patients (82%). Of these, 93 had infiltrating lobular carcinoma, 1089 had infiltrating ductal carcinoma, and 59 had tumors with mixed ductal and lobular features; these patients constitute the study population. The median follow-up time for surviving patients was 133 months. A comprehensive list of clinical and pathologic features was evaluated for all patients. Additional histologic features assessed for patients with infiltrating lobular carcinoma included histologic subtype, multifocal invasion, stromal desmoplasia, and the presence of signet ring cells. RESULTS: Five and 10-year crude results by site of first failure were similar for patients with infiltrating lobular, infiltrating ductal, and mixed histology. In particular, the 10-year crude local recurrence rates were 15%, 13%, and 13% for patients with infiltrating lobular, infiltrating ductal, and mixed histology, respectively. Ten-year distant/regional recurrence rates were 22%, 23%, and 20% for the three groups, respectively. In addition, the 10-year crude contralateral breast cancer rates were 4%, 13% and 6% for patients with infiltrating lobular, infiltrating ductal and mixed histology, respectively. In a multiple regression analysis which included established prognostic factors, histologic type was not significantly associated with either survival or time to recurrence. CONCLUSIONS: Patients with infiltrating lobular carcinoma have a similar outcome following CS and RT to patients with infiltrating ductal carcinoma and to patients with tumors that have mixed ductal and lobular features. We conclude that the presence of infiltrating lobular histology should not influence decisions regarding local therapy in patients with Stage I and II breast cancer.

Aged↗

PubMed2000

Repetitive self-injurious behavior: a neuropsychiatric perspective and review of pharmacologic treatments.

The phenomenology, pathophysiology, and psychopharmacology of repetitive self-injurious behavior (rSIB) are reviewed. Although numerous neurotransmitter systems are thought to be involved in the initiation and maintenance of rSIB, the majority of clinical studies attend to the role of serotonin or endogenous opioids. This focus has emerged from a conceptualization of rSIB as a problem of impulse control (primarily mediated by serotonin) and/or as a maladaptive pain-related behavior (ultimately mediated by opioids). A developmental perspective of rSIB is emphasized, highlighting the biased prevalence of rSIB among patients with mental retardation and severe personality disorders and the significance of critical developmental events leading to pathology in "pedagogical" neural circuits. A novel typology is offered in an effort to better match interventions with rSIB subtypes. Achievement of this ultimate goal however, must await further research.

Adult↗

PubMed2001

A comparative study of metastatic renal cell carcinoma with correlation to subtype and primary tumor.

Clear cell (CRCC), papillary (PRCC) and chromophobe (CHRC) renal cell carcinoma (RCC) are the three most frequent subtypes of RCC. The rate and distribution of their metastatic lesions have not been well documented. We compared metastatic RCC according to subtype and primary tumor characteristics to better understand their behavior and to aid in the diagnosis of metastatic RCC. Pathology reports and clinical charts related to 283 CRCC, 48 PRCC and 13 CHRCC, including their respective sarcomatoid variants, were reviewed. A hundred and thirty-seven CRCC, 5 PRCC and 1 CHRCC with metastases were identified. CRCC and non-CRCC (PRCC and CHRCC) had different patterns of metastasis and primary tumor growth. CRCC metastases were predominantly distributed in lungs, bone, brain, lymph nodes, and adrenal glands. The associated primary CRCC measured 1.5 to 15 cm, were of all grades and stages, and were often associated with invasion of small or large veins. Three PRCC had regional lymph node metastases, 1 PRCC had both regional and mediastinal lymph node metastases. Bone metastasis was present in 1 case each of PRCC and CHRCC. One PRCC with metastasis solely to regional nodes measured 4 cm. The other 4 cases of PRCC with regional lymph node and/or distant metastases as well as the CHRCC with distant metastases were greater than 8 cm in diameter. In metastasizing and non-metastasizing non-CRCC, invasion of small veins was rare and invasion of renal veins was not seen. We cannot comment with any certainty on the metastatic behavior of CHRCC. In our experience, PRCC tend to loco-regional invasion with lymph node spread. They have a low potential for vascular invasion and distant metastases that likely occur only at late stages of the disease. CRCC has a propensity for vascular invasion and may be associated with distant metastasis at an early stage. Therefore, metastatic RCC at a distant location are most likely to be of CRCC origin than PRCC origin.

Adrenal Gland Neoplasms↗

PubMed2005

NAAG peptidase inhibitor reduces acute neuronal degeneration and astrocyte damage following lateral fluid percussion TBI in rats.

Traumatic brain injury (TBI) produces a rapid and excessive elevation in extracellular glutamate associated with excitotoxicity and secondary brain pathology. The peptide neurotransmitter Nacetylaspartylglutamate (NAAG) suppresses glutamate transmission through selective activation of presynaptic Group II metabotropic glutamate receptor subtype 3 (mGluR3). Thus, inhibition of NAAG peptidase activity and the prolong presence of synaptic NAAG were hypothesized to have significant potential for cellular protection following TBI. In the present study, a novel NAAG peptidase inhibitor, ZJ-43, was used in four different doses (0, 50, 100, or 150 mg/kg). Each dose was repeatedly administered i.p. (n=5/group) by multiple injections at three times (0 time, 8 h, 16 h) after moderate lateral fluid percussion TBI in the rat. An additional group was co-administered ZJ-43 (150 mg/kg) and the Group II mGluR antagonist, LY341495 (1 mg/kg), which was predicted to abolish any protective effects of ZJ-43. Rats were euthanized at 24 h after TBI, and brains were processed with a selective marker for degenerating neurons (Fluoro-Jade B) and a marker for astrocytes (GFAP). Ipsilateral neuronal degeneration and bilateral astrocyte loss in the CA2/3 regions of the hippocampus were quantified using stereological techniques. Compared with vehicle, ZJ-43 significantly reduced the number of the ipsilateral degenerating neurons (p<0.01) with the greatest neuroprotection at the 50 mg/kg dose. Moreover, LY341495 successfully abolished the protective effects of ZJ-43. 50 mg/kg of ZJ-43 also significantly reduced the ipsilateral astrocyte loss (p<0.05). We conclude that the NAAG peptidase inhibitor ZJ-43 is a potential novel strategy to reduce both neuronal and astrocyte damage associated with the glutamate excitotoxicity after TBI.

Animals↗

PubMed1997

Lymphangioma-like variant of Kaposi's sarcoma: clinicopathologic study of seven cases with review of the literature.

The clinical and pathological features of seven cases of lymphangioma-like Kaposi's sarcoma (KS) are reported. As with the other subtypes of KS, the lymphangioma-like variant occurs more often in men aged 59-80 years. Clinically, the lesion appears intermingled with the classical forms of KS, but a "bulla-like" appearance recognized in seven of 13 cases has been considered as a clinical hallmark of this variant. Although occasional cases have shown aggressive behavior, the most frequent clinical course is slowly progressive with localized or diffuse involvement of lower limbs. The histological pattern, characterized by permeation of dermal collagen by labyrinthine vascular channels lined by a flattened endothelium, must be differentiated from spindle cell hemangioendothelioma, low-grade angiosarcoma, targetoid hemosiderotic hemangioma, and benign lymphangioendothelioma.

Adult↗

PubMed2004

Cutaneous desmoplastic melanoma: reappraisal of morphologic heterogeneity and prognostic factors.

Desmoplastic melanoma (DM) is a variant of melanoma, which may be confused with nonmelanocytic benign or malignant spindle cell proliferations. The histologic hallmark of DM is the presence of fusiform melanocytes dispersed in a prominent collagenous stroma. Phenotypic heterogeneity of DM is underrecognized. Desmoplasia may be prominent throughout the entire tumor ("pure" DM) or represent a portion of an otherwise nondesmoplastic melanoma ("combined" DM). We reviewed melanomas with desmoplasia from 92 patients seen at a single institution between 1980 and 2002. Fifty-five of the tumors were pure DM. Thirty-seven were classified as combined. Mean follow-up of patients was 46 months for those alive at the last follow-up. Univariate analysis of clinical and pathologic parameters revealed four significant variables for disease-free survival: Clark level (IV vs. V; P = 0.005), DM subtype (pure vs. combined; P = 0.01), tumor mitotic rate (<1, 1-4, >4 mitoses/mm; P = 0.01), and tumor thickness (<1 mm, 1-4 mm, >4 mm; P = 0.02). Only histologic subtype (P = 0.02) and Clark level (P = 0.05) were independently significant by Cox regression analysis. Our results indicate that distinguishing pure from combined forms of DM is clinically relevant for prognosis (pure forms being associated with longer disease-specific survival). Failure to make this distinction may account for conflicting reports in the literature on the biologic behavior and prognosis of DM.

Adolescent↗

PubMed1991

Recurrent transient ischemic attacks and stroke in association with an internal carotid artery web.

Fibromuscular dysplasia is a nonatherosclerotic vascular disease that most commonly affects cervical carotid arteries at the C1-C2 level when cephalic arteries are involved. Several histopathologic and angiographic subtypes of fibromuscular dysplasia exist; most have a benign natural history. We describe the third reported case of a pathologically proven, symptomatic proximal internal carotid artery web and suggest that patients with this lesion are at a higher risk for stroke.

Adult↗

PubMed2003

Correlation between histologic staging, hepatitis C virus genotypes and clinical features in HCV chronic hepatitis: evidence of a new pattern.

Genome heterogeneity may be related to the wide variability of clinical and pathological features in hepatitis C virus (HCV)-related chronic liver disease. This paper addresses the possible association between HCV subtypes and clinical and histological features of chronically infected patients. Sixty-eight consecutive liver biopsies of chronic hepatitis constituted the basis of the study. HCV genotyping was performed on frozen tissue. Grading of necroinflammatory activity and staging of fibrosis were histologically assessed. Serologic HCV-RNA and liver function were assessed at the same time. All information was compared with clinical data including age, sex, HCV serology, and probable data and route of infection. Two cases were excluded as inadequate tissue was available. Five cases were negative to HCV-RNA in both serum and tissue. In 61 cases HCV RNA was present at the same time in serum and liver tissue. Forty-four patients were men (72%) and 17 (28%) were women. Two peaks of age were observed: 1 in the 4th decade of life, the 2nd in the 7th. The 2 groups had different HCV genotypes. Patients with genotypes 1b (mean age 50.7 years), 2c (mean age 61.3 years), and a subgroup of coinfections (mean age 60 years) were older than patients with genotypes 1a (mean age 35.5 years), 3 (mean age 36 years), and a subgroup of coinfections (mean age 33 years). Patients with genotypes 1b, 2, or 2c and a subgroup of coinfections more frequently had a history of blood transfusion and or surgical intervention dating up to 49 years previously. Patients with HCV 1a, 3, and a subgroup of coinfections frequently admitted a period of intravenous drug abuse. Patients with advanced liver disease, i.e., severe fibrosis and cirrhosis, showed the same 2 peaks of incidence: in the 4th and 7th decades of life, the first group mainly comprising patients with HCV types 1a and 3, the second, patients with HCV types 1b and 2c. Both these groups shared a clinical history of a long-standing infection. Two profiles of patients emerged. The largest group was composed of elderly patients, infected by HCV genotypes 1b or 2c, with a history of blood transfusion and/or surgery, presenting an advanced stage of liver disease (namely, severe fibrosis or cirrhosis). The second group was composed of younger patients, mainly in the 4th decade of life, infected by HCV types 3 or 1a, often presenting with chronic hepatitis in the stage of severe fibrosis or cirrhosis. The latter could be the profile of HCV infection in the near future.

Adult↗

PubMed2002

Dementia with Lewy bodies.

BACKGROUND: Dementia with Lewy bodies (DLB) is a common dementia subtype that has only been recognised in the past decade and that remains widely underdiagnosed. AIMS: To review the pathological and clinical features of DLB, to consider methods of investigation and diagnosis, and to recommend safe and effective management strategies. METHOD: A selective review was made of the key literature. RESULTS: Using operationalised criteria, DLB can be clinically diagnosed with an accuracy similar to that achieved for Alzheimer's disease or Parkinson's disease. Underdetection is largely due to poor definition of the criterion of cognitive fluctuation. Ancillary investigations, particularly neuroimaging, can aid in differential diagnosis. Extreme caution in the use of neuroleptic medication is advised. Cholinesterase inhibitors may be particularly effective in DLB. CONCLUSIONS: Clinicians should be aware of DLB as part of a spectrum of Lewy body disorders. Neuroleptic sensitivity reactions and good response to cholinergic therapies are important aspects of management.

Aged↗

PubMed1999

Regulation of angiogenic growth factors in the female reproductive tract by estrogens and progestins.

Proper regulation of angiogenesis and vascular permeability is essential for the physiological functioning of the female reproductive tract, and major health problems in women, such as dysfunctional uterine bleeding, endometriosis, and uterine cancer, involve a vascular component. There is a large body of literature that describes the effects of sex steroids on the vasculature of the reproductive tract, but far less is known about the molecular mechanisms that regulate these important actions. We hope that this minireview will help emphasize the need for mechanistic studies in this area to improve treatment and prevention of these major health problems in women. Specifically, we believe it will be important to 1) define the exact roles of FGF, VEGF, and other factors in physiological and pathological events in the reproductive tract and the cell types and receptors involved; 2) identify estrogen and progesterone receptor subtypes, the DNA elements, nuclear protein factors, and signaling pathways that mediate regulation of these genes by sex steroids; 3) elucidate any mechanisms of cross-talk between sex steroids and other regulatory factors in the overall regulation of FGF, VEGF, and other angiogenic/permeability factors; and 4) eventually understand how genetic polymorphisms of key regulatory elements affect angiogenesis and the regulation of vascular function in the female reproductive tract.

Animals↗

PubMed1999

Sarcomatoid carcinoma of the lung: a clinicopathologic study of 37 cases.

BACKGROUND: Spindle and giant cell carcinomas of the lung are rare subtypes and are regarded as one type of lung carcinoma, termed pleomorphic carcinoma in the Armed Forces Institute of Pathology classification. This classification is different from the World Health Organization classification. METHODS: Thirty-seven cases of sarcomatoid (spindle and/or giant cell) carcinoma of the lung were studied by light microscopy, conventional histochemistry, and immunohistochemistry to establish their clinical and histologic characteristics. RESULTS: The patient population was comprised of 29 men and 8 women ages 33-81 years. Seventeen patients died of their disease and there was no statistically significant difference in patient prognosis between sarcomatoid carcinoma and nonsarcomatoid carcinoma of the lung. Using light microscopy, 5 cases (13.5%) comprised entirely of sarcomatoid components without carcinomatous elements were classified as Group A. In the remaining 32 cases (86. 5%), classified as Group B, carcinomatous components were present (adenocarcinoma [18 cases; 48.7%], squamous cell carcinoma [8 cases; 21.6%], and large cell carcinoma [6 cases; 16.2%]). Sarcomatoid components were divided further into three categories: spindle cell type, giant cell type, and mixed spindle and giant cell type. Immunohistochemically, the sarcomatoid components of all 37 cases were positive for cytokeratins. Statistically, there was no significant prognostic difference between the 37 cases of sarcomatoid carcinoma and 647 cases of nonsarcomatoid, nonsmall cell carcinoma of the lung (P = 0.8537). CONCLUSIONS: The sarcomatoid portions in all sarcomatoid carcinomas in the current study showed an epithelial differentiation, and there was no apparent difference in biologic behavior between sarcomatoid carcinoma and ordinary lung carcinoma.

Adult↗

PubMed2006

Thymomas: clinical-pathological correlations.

AIM: Since World Health Organization (WHO) histologic typing of tumors of the thymus publication in 1999 only a few studies correlated this classification with the clinical features of the patients. We present the results of a retrospective analysis on patients, operated on for a thymoma, whose specimens were available, to compare the WHO thymoma histologic classification to the clinical behavior of the tumors. METHODS: The specimens of 69 patients, who underwent surgical treatment between 1983 and 1998, were analyzed, comparing the clinical features of the patients and the hystological typing of the neoplasm, according to the WHO classification. A survival analysis of clinical and pathological prognostic factors was carried out. RESULTS: The incidence of thymus-related syndrome was related to the histological subtype and increases progressively from A to B3, while in C subtype the incidence was nihl. With a mean follow-up of 108 months (range 54-239 months), we experienced 6 intrathoracic recurrencies, 3 of those were intrapleuric and 3 mediastinal. At the last follow-up, 52 patients were alive; 1 with disease. Five deaths were related to the tumor (2 mediastinal and 3 intrapleuric relapses). Actuarial five-year and ten-year survival was 95% and 88.9%. Because of the absence of deaths related to thymomas in most samples it was not possible to perform a comparison among different histological types and different clinical stages. CONCLUSIONS: The WHO histologic classification seems to correlate with the incidence of thymus related syndromes and the clinical stage of Masaoka. Despite the higher incidence of recurrences in type B3 and C thymoma the WHO classification did not prove to be a prognostic factor.

Adult↗

PubMed1990

HLA-antigen frequencies in patients with progressive systemic sclerosis and morphea.

A possible HLA disease association was investigated in 40 patients (38 female, 2 male) with progressive systemic sclerosis (PSS) and 42 patients (32 female, 10 male) with morphea. The HLA A, B, C, DR phenotypes of patients were compared with 193 healthy controls. The following relative risk (RR) values were determined in PSS: A1 (1.38), A2 (1.39), B8 (1.67), B15 (3.22), DRw8 (6.30) and in morphea patients: A3 (1.43), B7 (1.39), B40 (1.81), Bw60 (2.49), DR2 (2.38) and DRw8 (2.55), indication a relatively weak, HLA-linked genetic predisposition for the manifestation of the disease. The HLA "risk" antigens for the two clinically different subtypes of the disease are also different: raised A1/B8 frequencies, like in our PSS group, correlate with a high, pathological immune response (autoimmune disorders). In contrast, A3/B7/DR2 prevalence, like in our morphea group, correlates with a low immune response. HLA typing may contribute to clinical differential diagnosis and possibly also prognosis.

Adult↗

PubMed1990

[A clinical and pathological study of small renal cell carcinomas].

Ten cases of a small renal cell carcinoma having a tumor that was 3 cm or less have been studied both clinically and pathologically. In nine of the 10 cases, the tumor had been detected incidentally, and all 9 were asymptomatic. Renal lesion were diagnosed all of the 10 cases by computed tomography and in 9 cases by ultrasonography. The pathological characteristics of small renal cell carcinoma are characterized by an expansive development, an alveolar structure, a clear cell subtype, a low grade nuclear atypism, and a general lack of infiltration. The postoperative follow up period was 20 months on average, and all patients had survived with no appearance of a new lesion.

Adult↗

PubMed2005

Personality subtypes in eating disorders: validation of a classification in a naturalistic sample.

BACKGROUND: Research has identified three personality subtypes in patients with eating disorders: emotionally dysregulated, constricted and high-functioning/perfectionistic. AIMS: To see whether the subtypes are distinguished in ways indicative of valid classification, notably in patterns of adaptive functioning, comorbidity, treatment response and therapeutic interventions. METHOD: A random sample of experienced clinicians provided data on 145 patients with bulimic symptoms, including data on eating disorder symptoms, DSM-IV comorbidity, personality pathology, treatment response and treatment interventions. RESULTS: Patients categorised as dysregulated had the poorest functioning, most comorbidity and worst outcome, followed by patients in the constricted and high-functioning groups. The three subtypes elicited different therapeutic interventions and accounted for substantial incremental variance in outcome, holding constant the severity of eating disorder symptoms and presence of other Axis I disorders. CONCLUSIONS: The data provide accumulating evidence for the validity of three personality subtypes in patients with eating disorders.

Adolescent↗

PubMed1999

Role of norepinephrine in the pathophysiology and treatment of mood disorders.

For four decades, norepinephrine (NE) has been postulated to play an important, possibly primary, role in the pathophysiology and subsequent treatment of mood disorders. The long-held hypothesis was that depression and pathological elation are direct functions of low and high activity of norepinephrine-containing neurons, respectively. Decades of research in this field have been devoted to further clarifying this relationship. However, there continues to be inconsistencies in the data, with different studies finding significant differences in NE metabolites and changes in receptor populations. Furthermore, antidepressants that do not act directly on the NE system appear to be quite effective in the treatment of depression. Although differential NE activity and treatment response may be partially due to different subtypes of depression, this clearly does not explain all the data. This review attempts to consolidate the relevant physiology of the NE system with the pathological changes found in depression. Norepinephrine clearly has an important role in this disease, but absolute changes in its activity are less likely to be the primary cause of the disorder. Evidence for dysregulation of the locus ceruleus-NE system in depression is quite apparent, however, contributing to disrupted attention, concentration, memory, arousal, and sleep. Homeostatic changes likely occur after chronic treatment with antidepressants, allowing a new regulatory state to occur in which NE modulation is once again effective. The availability of new tools such as selective ligands for the NE transporter that can be utilized with positron emission tomography imaging will undoubtedly advance the field.

Antidepressive Agents↗

PubMedDate not supplied

Primary mediastinal lymphoma: characteristic features of the various histological subtypes on CT.

OBJECTIVE: To assess the characteristic features of the primary mediastinal lymphoma (PML) on CT and to test the relationship between CT findings and the likelihood of the 3 most common subtypes (Hodgkin lymphoma [HL], mediastinal diffuse large B-cell lymphoma [Med-DLBCL], and precursor T-cell lymphoblastic lymphoma [T-LBL]). METHODS: Sixty-six consecutive patients with pathologically proven PML including 29 patients with HL, 21 with Med-DLBCL, and 16 with T-LBL underwent CT prior to therapy. CT scans were independently reviewed by 2 radiologists who were blinded to the pathologic diagnosis for the following considerations: pattern of involvement (i.e., morphologic features, mass size, and contrast enhancement pattern), and ancillary findings at other sites including neck, abdomen, and pelvis. Interobserver agreement was measured by Kappa statistics, and independent predictors were calculated using multiple logistic regression analysis for determining the likelihood of the subtypes based on CT. RESULTS: Characteristic features of HL included irregular contour of the anterior mediastinal mass (20 of 29, 69%) and high prevalence of associated mediastinal lymphadenopathy (28 of 29, 97%). Characteristic features of Med-DLBCL included regular contour (14 of 21, 67%) and absence of cervical and abdominal lymphadenopathy (0 of 21). Characteristic features of T-LBL included regular contour (12 of 16, 75%) and high prevalence of cervical (9 of 16, 56%) and abdominal (6 of 16, 38%) lymphadenopathy and splenomegaly (11 of 16, 69%). CT findings independently associated with increased likelihood of HL were surface lobulation (P <0.01), the absence of vascular involvement (P <0.01), or pleural effusion (P <0.05). The presence of vascular involvement was associated with increased likelihood of Med-DLBCL (P <0.001). Furthermore, CT findings including the presence of cervical lymph nodes or inguinal lymph nodes (P <0.001), the presence of pericardial effusion (P <0.05), and the absence of surface lobulation (P <0.05) were significantly associated with the likelihood of T-LBL. CONCLUSION: The various histologic subtypes of PML have characteristic manifestations in the neck, chest, and abdomen, which allow their distinction on CT.

Adolescent↗

PubMed1994

Pituitary and hypothalamic somatostatin receptor subtype messenger ribonucleic acid expression in the food-deprived and diabetic rat.

Prolonged food deprivation (FD) and streptozocin-induced diabetes (STZ diabetes) in the rat result in abolition of GH secretory episodes. We have previously shown that hypothalamic prepro-GRF messenger RNA (mRNA) expression is markedly reduced in the hypothalamus of FD and STZ diabetic rats, with no change in prepro-somatostatin (SRIF) mRNA and suggested that reduced GRF and increased SRIF tone explained the loss of GH secretion in FD and STZ diabetes. Altered SRIF peptide expression has been implicated in many physiological and pathological states; however, information on the regulation of SRIF receptor (SSTR) expression is lacking. Therefore, we examined the expression of mRNA for the five recently cloned SSTR subtypes in the pituitary and hypothalamus of FD and STZ diabetic rats. In addition, we measured SRIF binding to pituitary membranes of FD rats. SSTR1, SSTR2, and SSTR3 mRNA expression was reduced 80% in the pituitary of FD rats vs. fed controls, whereas pituitary levels of SSTR4 and SSTR5 mRNA were unaffected. The pituitary plasma membrane SSTR concentration was reduced over 50% in FD vs. fed animals. However, hypothalamic levels of the five isoforms were unchanged. In STZ diabetes, pituitary SSTR1, SSTR2, and SSTR3 mRNA expression was reduced 50-80%, with levels of SSTR1 partially restored by insulin, whereas SSTR4 mRNA was unchanged. In contrast to the effect of FD, SSTR5 mRNA levels were reduced 70% in the pituitary and 30% in the hypothalamus of STZ diabetic rats, with complete restoration by insulin. Thus, SSTR subtype mRNA expression is differentially regulated in two models of GH deficiency in the rat, FD and STZ diabetes. As chronic exposure to SRIF results in desensitization of transfected SSTR2 and SSTR3, and SSTR binding is decreased in FD and STZ diabetic rats, the possibility exists that the pituitary changes result from continued exposure to SRIF. In the hypothalamus, however, regulation appears more complex. These data support a role of increased SRIF with decreased GRF in mediating the loss of GH secretion in FD and diabetes.

Animals↗