Leptin and leptin receptor expression in rat and mouse pituitary cells

Leptin is a circulating hormone secreted mainly by adipose tissue. Recent studies have shown leptin production by other tissues, including the placenta, stomach, and mammary tissues. Various reports have suggested that the anterior pituitary may have a role in the regulatory effects of leptin. We recently localized leptin in the human anterior pituitary, but analysis of leptin in rodent pituitary has not been previously reported. In this study we examined rat and mouse pituitary tissues and various cell lines for leptin by RT-PCR, immunohistochemistry, and Western blotting. Leptin receptor messenger RNA was also examined in these tissues by RT-PCR. Leptin was present in a small percentage of rat (4.8 +/- 0.7%) and mouse (7 +/- 2%) pituitary cells. Colocalization studies with leptin and pituitary hormones showed leptin expression mainly in TSH cells (24 +/- 2% of TSH cells in the rat pituitary and 31 +/- 1% of TSH cells in the mouse pituitary). A folliculo-stellate (FS) cell line, TtT/GF, also expressed leptin. The long isoform of leptin receptor (OB-Rb) was present in normal pituitary and in various pituitary cell lines, including FS, GH3, and alphaT3-1 cells. Treatment of GH3 and FS cells with leptin (1 x 10(-8) M) inhibited cell proliferation assessed by [3H]thymidine incorporation in GH3, but not in FS, cells. These findings show for the first time that leptin is expressed in rat and mouse anterior pituitaries mainly by TSH cells and by a mouse FS cell line. The finding of leptin and of the long isoform of leptin receptor in normal rat and mouse pituitaries and in various cell lines implicates an autocrine/paracrine loop in the production and regulation of leptin and leptin receptor in the rodent pituitary.     

Expression of epidermal growth factor receptor in neoplastic pituitary cells: evidence for a role in corticotropinoma cells

The oncogenic effects of epidermal growth factor (EGF) have long been established. EGF receptor (EGFr) is overexpressed in many types of tumors and constitutes a target for cancer treatment. The pituitary gland is a target of EGF action and it is very likely that EGFr plays a role in pituitary tumor formation and progression. However, there is a controversy in the literature concerning EGFr expression in the different types of pituitary adenomas. In the present study we investigated the expression pattern of the wild type EGFr (EGFrWT) and the constitutively active variant III (EGFrvIII) at the mRNA and protein levels in a large series of pituitary tumors. EGFrWT was found in a high percentage of hormone-secreting tumors, but only in a small fraction of non-functioning pituitary adenomas, while no expression of the EGFrvIII could be detected by nested RT-PCR in any tumor. Among the hormone-secreting adenomas, the highest incidence of EGFr expression was found in Cushing's pituitary adenomas. Furthermore, immunohistochemistry for the phosphorylated EGFr revealed the presence of activated EGFr in most Cushing's adenomas, compared with most pituitary adenomas. Taking into account that downregulation of p27/Kip1 plays a significant role in corticotrope tumorigenesis and that EGFr mitogenic signaling results in decreased p27/Kip1, we searched for a correlation between EGFr expression and p27/Kip1 levels in corticotropinomas. Low p27/Kip1 immunoreactivity was observed in corticotropinomas expressing EGFr. On the other hand, somatotropinomas expressing EGFr had high p27/Kip1 immunoreactivity. These data suggest a corticotrope-specific phenomenon and indicate that EGFr may have a role in the unbalanced growth of corticotrope tumoral cells.     

Leptin upregulates beta3-integrin expression and interleukin-1beta, upregulates leptin and leptin receptor expression in human endometrial epithelial cell cultures

Human endometrium and endometrial epithelial cells (EECs) either cultured alone or cocultured with human embryos express leptin and leptin receptor. This study compares the effect of leptin with that of interleukin-1β (IL-1β) on the expression of β3-EEC integrin, a marker of endometrial receptivity. Both cytokines increased the expression of β3-EEC at concentrations in the range of 0.06–3 nM; however, leptin exhibited a significantly greater effect than IL-1β. We also determined the regulatory effects of IL-1β on leptin secretion and on the expression of leptin and leptin receptor at the protein level in both EEC and endometrial stromal cell (ESC) cultures. In EEC cultures, IL-1β upregulated secretion of leptin and expression of both leptin and leptin receptors. No effect of IL-1β was found in the ESC cultures. However, leptin exhibited marginal upregulation of leptin receptor. The upregulation of β3-integrin and leptin/leptin receptor expression by IL-1β in EEC cultures indicates that both cytokines may be implicated in embryonic-maternal cross-talk during the early phase of human implantation. Our present data also raise the possibility that leptin is an endometrial molecular effector of IL-1β action on β3-integrin upregulation. Thus, a new role for leptin in human reproduction as an autocrine/paracrine regulator of endometrial receptivity is proposed.     

Leptin and leptin receptor expression in the rat ovary

Leptin is an important satiety hormone and reproductive regulator and is found, along with its receptors, throughout the ovary. To date, the changes in ovarian expression of both of these proteins throughout the estrous cycle has not been studied, and the examination of protein expression has not distinguished between different forms of the receptor. In this study leptin mRNA expression in the immature gonadotropin-primed rat ovary increased 3-fold after human chorionic gonadotropin administration, followed by a dramatic increase in mRNA for both the short form (Ob-Ra) and the long form (Ob-Rb) of the leptin receptor (approximately 8- and 7-fold, respectively). A corresponding increase in mRNA expression of the receptor was not observed in isolated preovulatory follicles. Using immunohistochemistry, we observed protein expression of the long form of the leptin receptor (Ob-Rb) in the ovary, with high intensities observed in oocytes and endothelial cells as well as thecal cells and corpora lutea. These results suggest that ovarian expression of leptin and its receptor is regulated across the cycle by gonadotropins, with peak expression at ovulation, indicating a possible involvement in oocyte maturation, angiogenesis, follicle rupture, or subsequent corpus luteum formation.     

Activin effects on neoplastic proliferation of human pituitary tumors

Factors underlying growth regulation in human pituitary tumors are largely unknown. Activin functions as an antiproliferative cytokine in a number of cell types and is endogenously expressed in normal and neoplastic human pituicytes. We investigated the effect of activin on proliferation in 16 clinically nonfunctioning pituitary adenomas in primary culture. Treatment for 24 h with activin (0-10 ng/mL) significantly inhibited cell proliferation in 5 tumors (P < 0.05), as determined by [3H]thymidine incorporation. In 9 tumors, we studied regulation of the cyclin-dependent kinase inhibitor p21WAF1/cip1 as a potential activin mediator. In tumors with activin-inhibited proliferation, p21WAF1/cip1 gene expression was up-regulated after 4 h in a dose-dependent manner (0-100 ng/mL). We also investigated tumor expression of follistatin messenger ribonucleic acid, an activin-binding protein with two isoforms of different potencies. In contrast to normal pituitary tissue, only four tumors expressed both follistatin isoforms, and three tumors expressed only the less potent form. Tumors in which activin induced antiproliferative responses showed diminished or no follistatin messenger ribonucleic acid expression compared to normal pituitary. These data indicate that activin has an antiproliferative effect in a subgroup of human pituitary tumors.     

The expression of the pituitary growth hormone-releasing hormone receptor and its splice variants in normal and neoplastic human tissues

Various attempts to detect human pituitary growth hormone-releasing hormone receptor (pGHRH-R) in neoplastic extrapituitary tissues have thus far failed. Recently, four splice variants (SVs) of GHRH-R have been described, of which SV1 has the highest structural homology to pGHRH-R and likely plays a role in tumor growth. The aim of this study was to reinvestigate whether human tumors and normal human extrapituitary tissues express the pGHRH-R and to corroborate our previous findings on its SVs. Thus, we developed a real-time PCR method for the detection of the mRNA for the pGHRH-R, its SVs, and the GHRH peptide. Using real-time PCR, Western blotting, and radioligand-binding assays, we detected the mRNA for pGHRH-R and pGHRH-R protein in various human cancer cell lines grown in nude mice and in surgical specimens of human lung cancers. The expression of mRNA for SVs of pGHRH-R and GHRH was likewise found in xenografts of human non-Hodgkin's lymphomas, pancreatic cancer, glioblastoma, small-cell lung carcinomas, and in human nonmalignant prostate, liver, lung, kidney, and pituitary. Western blots showed that these normal and malignant human tissues contain SV1 protein and immunoreactive GHRH. Our results demonstrate that some normal human tissues and tumors express mRNA and protein for the pGHRH-R and its splice variants. These findings confirm and extend the concept that GHRH and its receptors play an important role in the pathophysiology of human cancers.     

Thyrotrophin receptor protein expression in normal and adenomatous human pituitary

Thyrotrophin (TSH) synthesis and secretion is under the positive control of thyrotrophin releasing hormone and under the negative control of the thyroid hormones. However, it is hypothesised that TSH has a direct effect on the regulation of its own synthesis through an intrapituitary loop mediated by pituitary TSH receptors (TSH-R). The aim of this investigation was to study the expression of TSH-R in normal human pituitary at mRNA and protein levels, and to compare the pattern of protein expression between different pituitary adenomas. Using RT-PCR we were able to detect TSH-R mRNA in the normal pituitary, and immunohistochemical studies showed TSH-R protein expression in distinct areas of the anterior pituitary. Double immunostaining with antibodies against each of the intrapituitary hormones and S100 revealed that TSH-R protein is present in thyrotrophs and folliculostellate cells. Examination of 58 pituitary adenomas, including two clinically active and two clinically inactive thyrotroph adenomas, revealed TSH-R immunopositivity in only the two clinically inactive thyrotroph adenomas. This study shows, for the first time, the presence of TSH-R protein in the normal anterior pituitary and in a subset of thyrotroph adenomas. The expression of TSH-R in the thyrotroph and folliculostellate cell subpopulations provides preliminary evidence of a role for TSH in autocrine and paracrine regulatory pathways within the anterior pituitary gland.     

Leptin receptor and functional effects of leptin in human endothelial progenitor cells

Circulating endothelial progenitor cells (EPCs) may be involved in the maintenance of vascular homeostasis and their impairment may be conducive to vascular disease. We studied the role of an adipocyte-derived hormone, leptin, in the regulation of human EPC function. EPCs were grown from human circulating mononuclear cells. The presence of the leptin receptor and the functional effects of leptin in EPCs were investigated. EPCs stained positive for endothelial cell markers (Flk-1 and Tie-2 receptors) and the hematopoietic CD34 marker. The presence of the long form of the leptin receptor in EPCs was confirmed by Western blotting and with immunofluorescence. Leptin, at a physiological concentration of 10 ng/ml, significantly increased tube formation from 2.1+/-2.2 to 12.4+/-4.9 tubes/25 mm2. At a higher concentration of 100 ng/ml of leptin, tube formation was reduced compared to the lower concentration. This higher concentration of leptin also inhibited EPC migration, decreasing it from 0.45+/-0.14 to 0.28+/-0.12 mm/48 h. Leptin did not have any effect on EPC proliferation. In summary, the leptin receptor is present in human EPCs and leptin may affect EPC function, both in physiological and in hyperleptinemic conditions. These findings are relevant to leptin-mediated regulation of vasculogenesis in humans, and the association between hyperleptinemia and obesity with cardiovascular disease.     

Apoptosis: its role in pituitary development and neoplastic pituitary tissue

Apoptosis, also known as programmed cell death, is a phenomenon in which different stimuli trigger cellular mechanisms that culminate in death, in the absence of inflammatory cell response. Two different activation pathways are known, the intrinsic pathway (or mitochondrial) and extrinsic (or death-receptor pathway), both pathways trigger enzymatic reactions that lead cells to break up and be phagocytized by neighboring cells. This process is a common occurrence in physiological and pathological states, participating in the control of cell proliferation, differentiation and remodeling of organs. In the early steps of pituitary gland formation, numerous apoptotic cells are detected in the separation of Rathke’s pouch from the roof of oral ectoderm. In the distal part of the gland, which will form the adenohypophysis, the ratio of apoptosis was significantly lower. However, there is evidence that neoplastic pituitary cells undergo unbalance in genes that control apoptosis leading to uncontrolled cell growth. No direct evidence of apoptosis was found in the drugs used for tumors producing prolactin and growth hormone. In conclusion, an unbalancing in the apoptosis process is the boundary between development and tumor growth.     

Expression and function of sonic hedgehog pathway components in pituitary adenomas: evidence for a direct role in hormone secretion and cell proliferation

CONTEXT: Sonic hedgehog (Shh) belongs to a family of signaling proteins involved in development and has been recently implicated in cancer. Shh signaling is active in the corticotrophs of the adult pituitary gland, where it cross-talks with the CRH pathway and regulates ACTH secretion. Because developmental pathways are involved in pituitary tumorigenesis, we hypothesized that Shh may be important in pituitary tumors. OBJECTIVE: The objective of this study was to examine the expression and function of Shh-pathway components in pituitary adenomas. METHODS: Using immunohistochemistry, we determined the expression of Shh and its receptors Patched 1 (Ptc1) and Patched 2 (Ptc2) in 55 human pituitary adenomas compared with the normal pituitary gland. The AtT-20 and GH3 pituitary tumor cell lines were used as models for studying the role of Shh on cell proliferation and hormone secretion. The effect of Shh on hormone secretion was confirmed in primary cultures of normal rat pituitaries and human pituitary tumors. RESULTS: Ptc1 and Ptc2 were present, whereas Shh was down-regulated in pituitary adenomas and completely absent in Cushing tumors. Shh inhibited cell proliferation in AtT-20 corticotrophinoma cells and the Shh-specific inhibitor cyclopamine increased proliferation in GH3 mammosomatotrophinoma cells. On the other hand, exogenous administration of Shh increased hormone secretion from normal rat pituitaries, pituitary cell lines, and 10 different pituitary tumors. CONCLUSIONS: Our results suggest that Shh might maintain pituitary cells in a nonproliferative state. We conclude that Shh is a newly described hypophysiotropic cytokine and its down-regulation may be involved in the pathogenesis of pituitary adenomas.     

Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels.

Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU i.m.) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced androgens in male obesity.     

bcl-2 proto-oncogene expression in normal and neoplastic human myeloid cells.

The present study provides immunobiochemical and molecular data on the differentiation-linked expression of the bcl-2 proto-oncogene in normal and neoplastic myeloid cells. Using a recently developed monoclonal antibody (MoAb) to the bcl-2 molecule, staining of normal bone marrow myeloblasts, promyelocytes, and myelocytes, but neither monocytes nor most polymorphonuclear cells, was demonstrated. By two-color flow cytometric analysis, bcl-2 was evidenced in CD33+ and CD33+/CD34+ myeloid cells as well as in the more primitive CD33-/CD34+ population. The leukemic cell lines HL-60, KG1, GM-1, and K562 were bcl-2 positive together with 11 of 14 acute myeloid leukemias (AML) and three of three chronic myeloid leukemias (CML) in blast crises; six of seven CML were negative. Among myelodysplastic cases, augmentation of the bcl-2 positive myeloblastic compartment was found in refractory anemia with excess of blasts (RAEB) and in transformation (RAEB-t). Western blots of myeloid leukemias and control lymphocytes extracts evidenced an anti-bcl-2 immunoreactive band of the expected size (26 Kd). Moreover, the HL-60 and KG1 cell lines, both positive for the bcl-2 protein, exhibited the appropriate size bcl-2 mRNA (7.5 Kb). These findings clearly indicate that the bcl-2 gene is operative in myeloid cells and that the anti-bcl-2 MoAb identifies its product and not a cross-reactive epitope. Induction of HL-60 differentiation toward the monocytic and granulocytic pathways was accompanied by a marked decrease in bcl-2 mRNA and protein levels; bivariate flow cytometric analysis showed that the fraction becoming bcl-2 negative was in the G1 phase of the cell cycle. These data establish that the bcl-2 proto-oncogene is expressed on myeloid cells and their progenitors and is regulated in a differentiation-linked manner.     

The effects of adiponectin and leptin on human endothelial cell proliferation: a live-cell study

The effect of adiponectin and leptin on the proliferation of the human microvascular endothelial cell line (HMEC-1) was studied in the absence or presence of fetal bovine serum (FBS). The participation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt (PI-3K/Akt) pathways in this effect were evaluated. We studied the effect of both adipokines on the motility, mitosis, proliferation and cell death processes of HMEC-1 cells using live-cell imaging techniques. Adiponectin but not leptin further increased the proliferative effect induced by FBS on HMEC-1. This effect seems to be the consequence of an increase in the mitotic index in adiponectin-treated cells when compared to untreated ones. The presence of either the mitogen-activated protein kinase (MAPK) inhibitor (PD98059), or PI-3K inhibitor (LY294002), reduced the effect of adiponectin in a dose-dependent manner. Neither adipokine was able to affect HMEC-1 proliferation in FBS-free conditions. Duration of mitosis, cell motility and the cell death process were similar in all conditions. These data suggest that adiponectin and leptin exert different effects on endothelial cell function. Adiponectin was able to potentiate proliferation of HMEC-1. This effect involves the activation of both PI3-K/Akt and ERK/MAPK pathways. However, it seems to exert minimal effects on HMEC-1 function in the case of leptin.     

The role of leptin in human obesity and disease: a review of current evidence

PURPOSE: To review recent advances in the pathophysiology and potential clinical applications of leptin, an adipose tissue-derived hormone. DATA SOURCES: A MEDLINE search of the literature on leptin and the bibliographies of relevant papers. STUDY SELECTION: All 1320 publications on leptin. DATA EXTRACTION: All identified articles were reviewed. Cited publications were selected on the basis of study quality and relevance to human obesity and disease. DATA SYNTHESIS: Leptin is a 16-kilodalton adipocyte-derived hormone that circulates in the serum in the free and bound form. Serum levels of leptin reflect the amount of energy stored in adipose tissue. Short-term energy imbalance as well as serum levels of several cytokines and hormones influence circulating leptin levels. Leptin acts by binding to specific receptors in the hypothalamus to alter the expression of several neuropeptides that regulate neuroendocrine function and energy intake and expenditure. Thus, leptin plays an important role in the pathogenesis of obesity and eating disorders and is thought to mediate the neuroendocrine response to food deprivation. Phase I and II trials recently showed that leptin administration to humans is safe, and ongoing phase III trials are assessing the efficacy of leptin as a treatment for obesity and related disorders. Availability of leptin or smaller and more soluble leptin analogues for clinical studies in humans is expected to significantly advance understanding of the mechanisms underlying energy homeostasis in humans. CONCLUSIONS: Leptin is significantly broadening our understanding of the mechanisms underlying neuroendocrine function, body weight, and energy homeostasis. Elucidation of these mechanisms is expected to result in the development of novel therapeutic approaches for obesity and eating disorders.     

Normal human pituitary gland and pituitary adenomas express cannabinoid receptor type 1 and synthesize endogenous cannabinoids: first evidence for a direct role of cannabinoids on hormone modulation at the human pituitary level

Little is known about the expression and function of cannabinoid receptor type 1 (CB1) in the human pituitary gland. The aim of this study was to investigate CB1 expression in human normal and tumoral pituitaries by in situ hybridization and immunohistochemistry using an antibody against CB1. CB1 was found in corticotrophs, mammotrophs, somatotrophs, and folliculostellate cells in the anterior lobe of normal pituitary. After examination of 42 pituitary adenomas, CB1 was detected in acromegaly-associated pituitary adenomas, Cushing's adenomas, and prolactinomas, whereas faint or no expression was found in nonfunctioning pituitary adenomas. Experiments with cultured pituitary adenoma cells showed that the CB1 agonist WIN 55,212--2 inhibited GH secretion in most of acromegaly-associated pituitary adenomas tested and that the CB1 antagonist SR 141716A was generally able to reverse this effect. Moreover, WIN 55,212--2 was able to suppress GHRH-stimulated GH release, and this effect was not blocked by coincubation with SR 141716A, possibly indicating a non-CB1-mediated effect. In contrast, WIN 55,212--2 was ineffective on GH-releasing peptide-stimulated GH release. In four Cushing's adenomas tested, WIN 55,212--2 was not able to modify basal ACTH secretion. However, simultaneous application of CRF and WIN 55,212--2 resulted in a synergistic effect on ACTH secretion, and this effect could be abolished by SR 141716A, demonstrating a CB1-mediated effect. In the single case of prolactinomas tested, WIN 55,212--2 was able to inhibit basal secretion of PRL. Finally, the presence of endocannabinoids (anandamide and 2-arachidonoylglycerol) was investigated in normal and tumoral pituitaries. All tumoral samples had higher contents of anandamide and 2-arachidonoylglycerol compared with the normal hypophysis. Moreover, endocannabinoid content in the different pituitary adenomas correlated with the presence of CB1, being elevated in the tumoral samples positive for CB1 and lower in the samples in which no or low levels of CB1 were found. The results of this study point to a direct role of cannabinoids in the regulation of human pituitary hormone secretion.     

In vitro effect of human recombinant leptin and expression of leptin receptors on growth hormone-secreting human pituitary adenomas

OBJECTIVES: Untreated growth hormone deficiency (GHD) is implicated in the increased cardiovascular risk associated with adult hypopituitarism. Oxidative stress, predisposing to lipid peroxidation, may be an important mediator of endothelial dysfunction, a pro-atherogenic state associated with adult GHD. DESIGN AND PATIENTS: In a randomized, double-blind, placebo-controlled study we investigated the effects of GH replacement on low-density lipoprotein (LDL) oxidation and neutrophil superoxide (O(-)(2)) generating capacity in 32 GHD adults (19 males, 13 females; age range 19-64 years) over 3 months. Thirty age- and sex-matched healthy controls were also studied. MEASUREMENTS: Lipid hydroperoxides (HPOs) in plasma were measured using the ferrous oxidation with xylenol orange (FOX) assay. The susceptibility of LDL to oxidation was assessed by the copper-catalysed lag phase of LDL oxidation. Neutrophil O(-)(2)- generating capacity was assessed by a lucigenin-based chemiluminescent assay of NADPH oxidase activity. Body composition was assessed using bioelectrical impedance analysis. RESULTS: Compared to controls, GHD subjects had higher LDL cholesterol (4.0 +/- 0.8 vs. 3.5 +/- 0.9 mmol/l, P < 0.01) and higher triglyceride concentrations (2.3 +/- 1.5 vs. 1.1 +/- 0.7 mmol/l, P < 0.001) but lower HDL cholesterol (1.1 +/- 0.3 mmol/l vs. 1.4 +/- 0.4 mmol/l, P < 0.01), lower levels of HPOs (0.72 +/- 0.35 vs. 0.92 +/- 0.20 microm, P < 0.01) and lower basal (2.5 +/- 1.5 vs. 4.5 +/- 2.3 mV/5 x 10(5) neutrophils, P < 0.01) and peak post-activation levels (23.2 +/- 11.1 vs. 34.4 +/- 15.6 mV/5 x 10(5) neutrophils, P < 0.01) of neutrophil O(-)(2)- generation. GH replacement resulted in an increase in HPOs from 0.70 +/- 0.39 to 0.86 +/- 0.19 microm (P < 0.05), although there was no change in the lag time of LDL oxidation. Neutrophil O(-)(2)- generating capacity was enhanced with a rise in basal O(-)(2)- generation from 2.8 +/- 1.4 to 5.4 +/- 4.6 mV/5 x 10(5) neutrophils (P < 0.05) and in peak post-activation O(-)(2)- generation from 21.9 +/- 9.5 to 35.8 +/- 21.7 mV/5 x 10(5) neutrophils (P < 0.05). LDL cholesterol was reduced from 4.1 +/- 0.8 mmol/l to 3.5 +/- 0.8 mmol/l (P < 0.01). No significant changes in measured parameters occurred in the placebo group. CONCLUSIONS: Adult GHD is associated with reduced lipid peroxidation and impaired neutrophil O(-)(2)- generating capacity, both of which are reversible with GH replacement. Our data suggest that: (i) that oxidative stress is not a major feature of the pro-atherogenic state in hypopituitary adults with GHD and (ii) a role for GH in modulating neutrophil function and leucocyte-lipoprotein interactions.     

Expression of leptin receptor mRNA and the long form splice variant in human anterior pituitary and pituitary adenoma.

Expression of leptin receptor (OB-R) mRNA was detected in the human anterior pituitary as well as in ACTH-secreting and nonsecreting pituitary adenomas by RT-PCR with primers recognizing all receptor splice variants. Primers specific to the long splice variant of the leptin receptor (OB-Rb), containing the putative intracellular signalling domain, also revealed a strong expression in normal and adenomatous anterior pituitaries. These results indicate that the pituitary is a possible target tissue of leptin action and might be involved in leptin regulation of pituitary hormone secretion.