Normal gonadotropin production and fertility in gonadotrope-specific Bmpr1a knockout mice

Pituitary follicle-stimulating hormone (FSH) synthesis is regulated by transforming growth factorβsuperfamily ligands, most notably the activins and inhibins. Bone morphogenetic proteins (BMPs) also regulate FSHβ subunit (Fshb) expression in immortalized murine gonadotrope-like LβT2 cells and in primary murine or ovine primary pituitary cultures. BMP2 signals preferentially via the BMP type I receptor, BMPR1A, to stimulate murine Fshb transcription in vitro. Here, we used a Cre–lox approach to assess BMPR1A’s role in FSH synthesis in mice in vivo. Gonadotrope-specific Bmpr1a knockout animals developed normally and had reproductive organ weights comparable with those of controls. Knockouts were fertile, with normal serum gonadotropins and pituitary gonadotropin subunit mRNA expression. Cre-mediated recombination of the floxed Bmpr1a allele was efficient and specific, as indicated by PCR analysis of diverse tissues and isolated gonadotrope cells. Furthermore, BMP2 stimulation of inhibitor of DNA binding 3 expression was impaired in gonadotropes isolated from Bmpr1a knockout mice, confirming the loss of functional receptor protein in these cells. Treatment of purified gonadotropes with small-molecule inhibitors of BMPR1A (and the related receptors BMPR1B and ACVR1) suppressed Fshb mRNA expression, suggesting that an autocrine BMP-like molecule might regulate FSH synthesis. However, deletion of Bmpr1a and Acvr1 in cultured pituitary cells did not alter Fshb expression, indicating that the inhibitors had off-target effects. In sum, BMPs or related ligands acting via BMPR1A or ACVR1 are unlikely to play direct physiological roles in FSH synthesis by murine gonadotrope cells.

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Healing effects of curcumin nanoparticles in deep tissue injury mouse model.

Current Drug Delivery ◽

10.2174/1567201818666201214125237 ◽

2020 ◽

Vol 18 ◽

Author(s):

Zirui Zhang ◽

Shangcong Han ◽

Panpan Liu ◽

Xu Yang ◽

Jing Han ◽

...

Keyword(s):

Wound Healing ◽

Mrna Expression ◽

Tissue Injury ◽

Inflammatory Cells ◽

Pcr Analysis ◽

Protective Effects ◽

Deep Tissue ◽

Deep Tissue Injury

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

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C57BL/6JOlaHsd Mice with Tandem Deletion of the Multimerin 1 and Alpha-Synuclein Genes Have Impaired Platelet Function in Vivo and in Vitro That Can Be Corrected by Multimerin 1

Blood ◽

10.1182/blood.v112.11.3926.3926 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3926-3926 ◽

Cited By ~ 1

Author(s):

Subia Tasneem ◽

Adili Reheman ◽

Heyu Ni ◽

Catherine P.M. Hayward

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Knockout Mice ◽

Platelet Adhesion ◽

Thrombus Formation ◽

Alpha Synuclein ◽

Type I ◽

Significant Difference

Abstract Studies of mice with genetic deficiencies have provided important insights on the functions of many proteins in thrombosis and hemostasis. Recently, a strain of mice (C57BL/6JOlaHsd, an inbred strain of C57BL/6J) has been identified to have a spontaneous, tandem deletion of the multimerin 1 and α-synuclein genes, which are also adjacent genes on human chromosome 4q22. Multimerin 1 is an adhesive protein found in platelets and endothelial cells while α-synuclein is a protein found in the brain and in blood that is implicated in neurodegenerative diseases and exocytosis. In vitro, multimerin 1 supports platelet adhesion while α-synuclein inhibits α-granule release. We postulated that the loss of multimerin 1 and α-synuclein would alter platelet function and that recombinant human multimerin 1 might correct some of these abnormalities. We compared platelet adhesion, aggregation and thrombus formation in vitro and in vivo in C57BL/6JOlaHsd and C57BL/6 mice. Thrombus formation was studied by using the ferric-chloride injured mesenteric arteriole thrombosis model under intravital microscopy. We found that platelet adhesion, aggregation and thrombus formation in C57BL/6JOlaHsd were significantly impaired in comparison to control, C57BL/6 mice. The number of single platelets, deposited 3–5 minutes after injury, was significantly decreased in C57BL/6JOlaHsd mice (P <0.05, platelets/min: C57BL/6 = 157 ± 15, n=16; C57BL/6JOlaHsd = 77 ± 13, n=17). Moreover, thrombus formation in these mice was significantly delayed. Thrombi in C57BL/6JOlaHsd were unstable and easily dissolved, which resulted in significant delays (P<0.001) in vessel occlusion (mean occlusion times: C57BL/6 = 15.6 ± 1.2 min, n=16; C57BL/6JOlaHsd = 31.9 ± 2.1 min, n=17). We further tested platelet function in these mice by ADP and thrombin induced platelet aggregation using platelet rich plasma and gel-filtered platelets, respectively. Although no significant differences were seen with ADP aggregation, thrombin-induced platelet aggregation was significantly impaired in C57BL/6JOlaHsd mice. Platelet adhesion to type I collagen (evaluated using microcapillary chambers, perfused at 1500 s−1 with whole blood) was also impaired in C57BL/6JOlaHsd mice. However, platelets from C57BL/6JOlaHsd mice showed a normal pattern of agonist-induced release of α-granule P-selectin. Multimerin 1 corrected the in vitro aggregation and adhesion defects of C57BL/6JOlaHsd platelets. Furthermore, the transfusion of multimerin 1 into C57BL/6JOlaHsd mice corrected the impaired platelet deposition and thrombus formation in vivo. No significant difference was found in tail bleeding time between the two groups of mice. As α-synuclein knockout mice have a shortened time to thrombus formation (Circulation2007;116:II_76), the effects of multimerin 1 on impaired platelet function in C57BL/6JOlaHsd mice provide supportive evidence that multimerin 1 contributes to platelet adhesion and thrombus formation at the site of vessel injury. The findings suggest multimerin 1 knockout mice will be useful to explore platelet function. The first two authors and participating laboratories contributed equally to this study.

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Differential activation of the pituitary-adrenocortical axis after stress in the rat: use of two genetically selected lines (Roman low- and high-avoidance rats) as a model

Journal of Endocrinology ◽

10.1677/joe.0.1230477 ◽

1989 ◽

Vol 123 (3) ◽

pp. 477-485 ◽

Cited By ~ 60

Author(s):

C.-D. Walker ◽

R. W. Rivest ◽

M. J. Meaney ◽

M. L. Aubert

Keyword(s):

Glucocorticoid Receptor ◽

Conditioned Avoidance ◽

Plasma Corticosterone ◽

Type I ◽

Pituitary Cells ◽

Acth Secretion ◽

Rapid Acquisition ◽

Basal Plasma

ABSTRACT We have examined the activation of the pituitary-adrenal axis in two lines of rats, the Roman high (RHA)- and low (RLA)-avoidance rats known to be emotionally different. These rats are selected for rapid acquisition of a conditioned avoidance response (RHA) compared with failure to acquire this response (RLA). In this study the endocrine response (ACTH, corticosterone, aldosterone) of RLA and RHA rats to two types of stress was examined: exposure to openfield stress for 10 min (Op) or exposure to ether vapours for 3 min (E). Basal plasma ACTH concentrations were lower in RLA than in RHA rats (RLA: 110·8 ± 24·5 ng/l; RHA: 252·7 ± 60·8 ng/l, P<0·05) but the absolute values of ACTH reached after both types of stress were comparable between RLA and RHA rats. Plasma corticosterone and aldosterone under resting conditions were not different between RLA and RHA rats. Plasma corticosterone was higher in RLA following openfield stress (P<0·05) while no differences between RLA and RHA were observed after ether stress (RHA: basal = 66±14·nmol/l, Op =384± 55, E= 606± 75; RLA: basal=121±52, Op = 612 ±92, E= 698 ± 89). Stressinduced increases in plasma aldosterone were higher in the RLA line after both types of stress (RHA: basal = 175±36 pmol/l, Op = 546±53, E= 563± 47; RLA: basal = 272 ± 64, Op =1246 ± 91, E= 863 ± 72). Pituitary responsiveness to exogenous corticotrophinreleasing factor (CRF) in vivo and in vitro differed in the two lines: administration of ovine CRF (10 μg/kg body weight, i.p.) resulted in significant increases in ACTH secretion but the response was significantly lower in RHA rats (RHA: 511·1 ±41·5 ng/l; RLA: 831·4 ± 70·3 ng/l, P<0·01). Dispersed pituitary cells from the RHA line exhibited a smaller response to CRF (10 nmol/l) treatment in vitro compared with cells derived from the RLA rats (RHA: 750 ± 83% of control; RLA: 1374 ±79, P<0·01) suggesting differences in pituitary sensitivity to CRF between the two lines. Additional differences at the pituitary level were observed since the type II glucocorticoid receptor population in RHA rats was higher than in RLA rats (RHA: 246±13 fmol [3H]RU28362 bound/mg protein; RLA: 173±18, P<0·01). Similarly, hippocampal type I glucocorticoid receptor population was increased in RHA rats (RHA: 172·2 ± 8·3 fmol [3H]aldosterone bound/mg protein; RLA: 116·7±7·3, P< 0·01). It is concluded that first, differences in pituitary activity between RLA and RHA rats are distinct from changes observed at the adrenal level, secondly, increased stress-induced ACTH output in the RLA line is associated with enhanced pituitary sensitivity to CRF and possibly with diminished corticosterone inhibitory feedback action on CRF and ACTH secretion, and thirdly, the possible involvement of differences in the pattern of CRF secretion between RLA and RHA rats on resting pituitary ACTH secretion cannot be excluded. Journal of Endocrinology (1989) 123, 477–485

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Thymocyte-Synthesized Glucocorticoids Play a Role in Thymocyte Homeostasis and Are Down-Regulated by Adrenocorticotropic Hormone

Endocrinology ◽

10.1210/en.2009-0195 ◽

2009 ◽

Vol 150 (9) ◽

pp. 4163-4169 ◽

Cited By ~ 33

Author(s):

Shengjun Qiao ◽

Sam Okret ◽

Mikael Jondal

Keyword(s):

Mrna Expression ◽

Knockout Mice ◽

Corticosterone Level ◽

Double Knockout ◽

Hormone Production ◽

Down Regulation ◽

Adult Mice ◽

Messenger Molecule

Abstract Thymocytes from adult mice synthesize glucocorticoids (GCs), and some data indicate a role for this hormone production in thymic homeostasis. Here we present further support for this view by showing that the dramatic increase in thymocyte number seen after adrenalectomy (ADX) does not correlate with the decrease in systemic GCs but rather with an ACTH-mediated down-regulation of GC synthesis in thymocytes. High ACTH concentrations caused by ADX in wild-type mice down-regulated CYP11B1 mRNA expression, encoding the last enzyme required for corticosterone synthesis and as a consequence reduced GC synthesis in thymocytes. This was not seen in IL-1β/IL-18 double-knockout mice unable to respond to ADX with high ACTH levels. However, if ADX IL-1β/IL-18 double-knockout mice were treated with ACTH, this led to a down-regulation of CYP11B1 and GC synthesis in thymocytes. In addition, in vivo treatment of mice with the CYP11B1 antagonist metyrapone, without affecting the systemic corticosterone level, increased thymocyte numbers and in vitro treatment of isolated thymocytes prevented thymocyte loss. Furthermore, in vitro experiments showed that both ACTH and its receptor-induced second-messenger molecule cAMP down-regulated mRNA expression of critical enzymes in GC steroidogenesis and GC synthesis in thymocytes. We conclude that thymocyte-produced GCs are important for the homeostasis of adult mouse thymocytes and that high ACTH level, in contrast to stimulating GC synthesis in the adrenal glands, has the opposite effect in thymocytes.

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In vitro and in vivo tenocyte-protective effectiveness of dehydroepiandrosterone against high glucose-induced oxidative stress

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-04398-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Shintaro Mukohara ◽

Yutaka Mifune ◽

Atsuyuki Inui ◽

Hanako Nishimoto ◽

Takashi Kurosawa ◽

...

Keyword(s):

Oxidative Stress ◽

Matrix Metalloproteinase ◽

Protein Expression ◽

Achilles Tendon ◽

Mrna Expression ◽

High Glucose ◽

Control Group ◽

Type I

Abstract Background Dehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes. This study aimed to investigate the in vitro and in vivo protective effects of DHEA against high glucose-induced oxidative stress in tenocytes and tendons. Methods Tenocytes from normal Sprague-Dawley rats were cultured in low-glucose (LG) or high-glucose (HG) medium with or without DHEA. The experimental groups were: control group (LG without DHEA), LG with DHEA, HG without DHEA, and HG with DHEA. Reactive oxygen species (ROS) production, apoptosis, and messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, and interleukin-6 (IL-6) were determined. Further, diabetic rats were divided into a control group and a DHEA-injected group (DHEA group). NOX1 and NOX4 protein expression and mRNA expression of NOX1, NOX4, IL-6, matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-2, and type I and III collagens in the Achilles tendon were determined. Results In rat tenocytes, DHEA decreased the expression of NOX1 and IL-6, ROS accumulation, and apoptotic cells. In the diabetic rat Achilles tendon, NOX1 protein expression and mRNA expression of NOX1, IL-6, MMP-2, TIMP-2, and type III collagen were significantly lower while type I collagen expression was significantly higher in the DHEA group than in the control group. Conclusions DHEA showed antioxidant and anti-inflammatory effects both in vitro and in vivo. Moreover, DHEA improved tendon matrix synthesis and turnover, which are affected by hyperglycemic conditions. DHEA is a potential preventive drug for diabetic tendinopathy.

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NF-κB-Mediated Inhibition of Apoptosis Is Required for Encephalomyocarditis Virus Virulence: a Mechanism of Resistance in p50 Knockout Mice

Journal of Virology ◽

10.1128/jvi.72.7.5654-5660.1998 ◽

1998 ◽

Vol 72 (7) ◽

pp. 5654-5660 ◽

Cited By ~ 60

Author(s):

Edward M. Schwarz ◽

Cornel Badorff ◽

Timothy S. Hiura ◽

Rainer Wessely ◽

Annette Badorff ◽

...

Keyword(s):

Cell Lines ◽

Knockout Mice ◽

Defense Mechanism ◽

Encephalomyocarditis Virus ◽

Type I ◽

Double Knockout ◽

Physiological Importance ◽

Infected Cells

ABSTRACT Apoptosis is a central host defense mechanism to eliminate virus-infected cells. Activation of NF-κB suppresses apoptosis following some types of stimulation in vitro. To test the physiological importance of this pathway in vivo, we studied murine encephalomyocarditis virus (EMCV) infection in mice and cell lines defective in NF-κB1 (p50) signaling. As previously reported, we find that all p50 knockout (p50 −/−) mice survive an EMCV infection that readily kills normal mice. By introducing the p50 mutation into interferon (IFN) type I receptor knockout (IFNRI −/−) mice, we find that this resistance is not mediated by IFN-β as previously thought. While no IFNRI −/− mice survive, the double-knockout mice survive 60% of the time. The survival is tightly linked to the animals’ ability to clear the virus from the heart in vivo. Using murine embryonic fibroblasts (MEF) derived from wild-type, p50 −/−, and p65 −/− embryos, we found that NF-κB is not required for the replication cycle of EMCV. However, during these experiments we observed that p50 −/− and p65 −/− MEF infected with EMCV undergo enhanced, premature cytotoxicity. Upon examination of this cell death, we found that EMCV infection induced both plasma membrane and nuclear changes typical of apoptosis in all cell lines. These apoptotic processes occurred in an accelerated and pronounced way in the NF-κB-defective cells, as soon as 6 h after infection, when virus is beginning to be released. Previously, only the RelA (p65) subunit of NF-κB has been shown to play a role in suppressing apoptosis. In our studies, we find that p50 is equally important in suppressing apoptosis during EMCV infection. Additionally, we show that suppression of apoptosis by NF-κB1 is required for EMCV virulence in vivo. The attenuation in p50 −/− mice can be explained by rapid apoptosis of infected cells which allows host phagocytes to clear infected cells before the viral burst leading to a reduction of the viral burden and survival of the mice.

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In Vitro and in Vivo Tenocyte-protective Effectiveness of Dehydroepiandrosterone Against High Glucose-induced Oxidative Stress

10.21203/rs.3.rs-154654/v1 ◽

2021 ◽

Author(s):

Shintaro Mukohara ◽

Yutaka Mifune ◽

Atsuyuki Inui ◽

Hanako Nishimoto ◽

Takashi Kurosawa ◽

...

Keyword(s):

Oxidative Stress ◽

Matrix Metalloproteinase ◽

Protein Expression ◽

Achilles Tendon ◽

Mrna Expression ◽

High Glucose ◽

Control Group ◽

Type I

Abstract BackgroundDehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes. The aim of this study was to investigate the in vitro and in vivo protective effects of DHEA against high glucose-induced oxidative stress in tenocytes and tendons. Methods In an in vitro study, tenocytes from normal Sprague-Dawley rats were cultured in low-glucose (LG) or high-glucose (HG) medium with or without DHEA. The experimental groups were: control group (LG without DHEA), LG with DHEA, HG without DHEA, and HG with DHEA. Reactive oxygen species (ROS) production, apoptosis, and messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, and interleukin-6 (IL-6) were determined. In the in vivo study, diabetic rats were divided into a control group and a DHEA-injected group (DHEA group). NOX1 and NOX4 protein expression and mRNA expression of NOX1, NOX4, IL-6, matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-2, and type I and III collagens in the Achilles tendon were determined. Results In rat tenocytes, DHEA decreased the expression of NOX1 and IL-6, ROS accumulation, and apoptotic cells. In the diabetic rat Achilles tendon, NOX1 protein expression and mRNA expression of NOX1, IL-6, MMP-2, TIMP-2, and type III collagen were significantly lower, while type I collagen expression was significantly lower in the DHEA group.Conclusions DHEA showed antioxidant and anti-inflammatory effects both in vitro and in vivo. Moreover, DHEA improved tendon matrix synthesis and turnover which are affected by hyperglycemic conditions. DHEA could be a preventive drug for the diabetic tendinopathy.

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HPLC/MSn Profiling and Healing Activity of a Muco-Adhesive Formula of Salvadora persica against Acetic Acid-Induced Oral Ulcer in Rats

Nutrients ◽

10.3390/nu14010028 ◽

2021 ◽

Vol 14 (1) ◽

pp. 28

Author(s):

Nahla Ayoub ◽

Nadia Badr ◽

Saeed S. Al-Ghamdi ◽

Safaa Alsanosi ◽

Abdullah R. Alzahrani ◽

...

Keyword(s):

Acetic Acid ◽

Mrna Expression ◽

Ethyl Acetate Fraction ◽

Type I ◽

Salvadora Persica ◽

Sulphur Compounds ◽

Wide Range ◽

Anti Inflammatory

Salvadora persica L. (S. persica, Siwak) is an ethnic plant that is widely used for improving oral hygiene. This study aimed to provide a phytochemical profiling of S. persica ethyl acetate fraction (SPEAF) and to evaluate the healing activity of a muco-adhesive formula of the fraction against acetic acid-induced oral ulcers in rats. HPLC-ESI-QTOF-MS-MS analysis of SPEAF resulted in the tentative identification of 56 metabolites containing fatty acids (23%), urea derivatives (10.5%) and sulphur compounds (10%), in addition to several amides, polyphenols and organic acids (6.5%, 5% and 2%, respectively). For the first time, 19 compounds were identified from S. persica. In vitro and in vivo experiments indicated that the extract is non-toxic. SPEAF exhibited superior healing activities compared to both the negative and positive control groups on days 7 and 14 of tongue ulcer induction. This was confirmed by histopathological examinations of haematoxylin and eosin-stained (H&E) and Masson’s trichrome-stained tongue sections. Moreover, SPEAF showed potent anti-inflammatory activities, as evidenced by the inhibited expression of interleukin-6 (IL-6) and tumour necrosis alpha (TNF-α). Moreover, SPEAF exhibited potent antioxidant activity, as it prevented malondialdehyde (MDA) accumulation, reduced glutathione (GSH) depletion and superoxide dismutase (SOD) exhaustion. SPEAF significantly enhanced hydroxyproline tongue content and upregulated collagen type I alpha 1 (Col1A1) mRNA expression. SPEAF also improved angiogenesis, as shown by the increased mRNA expression of the angiopoietin-1 (Ang-1). In conclusion, S. persica has a wide range of secondary metabolites and ameliorates acetic acid-induced tongue ulcers in rats. This can be attributed, at least partly, to its anti-inflammatory, antioxidant, procollagen and angiogenic activities. These findings provide support and validity for the use of S. persica as a traditional and conventional treatment for oral disorders.

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NK3R Mediates the EGF-Induced SLα Secretion and mRNA Expression in Grass Carp Pituitary

International Journal of Molecular Sciences ◽

10.3390/ijms20010091 ◽

2018 ◽

Vol 20 (1) ◽

pp. 91 ◽

Cited By ~ 2

Author(s):

Xiangfeng Qin ◽

Cheng Ye ◽

Xiaoyun Zhou ◽

Jingyi Jia ◽

Shaohua Xu ◽

...

Keyword(s):

Mrna Expression ◽

Grass Carp ◽

Cell Function ◽

Cell Types ◽

Pituitary Cells ◽

Dependent Manner ◽

Lower Vertebrates ◽

Mrna And Protein Expression

Epidermal growth factor (EGF) is a potent regulator of cell function in many cell types. In mammals, the EGF/EGFR system played an important role in both pituitary physiology and pathology. However, it is not clear about the pituitary action of EGF in lower vertebrates. In this study, using grass carp as a model, we found that EGF could stimulate NK3R mRNA and protein expression through pituitary ErbB1 and ErbB2 coupled to MEK/ERK and PI3K/Akt/mTOR pathways. In addition, EGF could also induce pituitary somatolactin α (SLα) secretion and mRNA expression in a dose- and time-dependent manner in vivo and in vitro. The stimulatory actions of EGF on SLα mRNA expression were also mediated by PI3K/Akt/mTOR and MEK/ERK pathways coupled to ErbB1 and ErbB2 activation. Our previous study has reported that neurokinin B (NKB) could also induce SLα secretion and mRNA expression in carp pituitary cells. In the present study, interestingly, we found that EGF could significantly enhance NKB-induced SLα mRNA expression. Further studies found that NK3R antagonist SB222200 could block EGF-induced SLα mRNA expression, indicating an NK3R requirement. Furthermore, cAMP/PKA inhibitors and PLC/PKC inhibitors could both abolish EGF- and EGF+NKB-induced SLα mRNA expression, which further supported that EGF-induced SLα mRNA expression is NK3R dependent.

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In vitro and in vivo effects of ghrelin on luteinizing hormone and growth hormone release in goldfish

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00669.2003 ◽

2004 ◽

Vol 286 (6) ◽

pp. R1093-R1101 ◽

Cited By ~ 78

Author(s):

Suraj Unniappan ◽

Richard E. Peter

Keyword(s):

Growth Hormone ◽

Luteinizing Hormone ◽

Mrna Expression ◽

Pituitary Cells ◽

The Novel ◽

Serum Lh ◽

Lh Release ◽

In Vivo Effects

We studied the in vitro and in vivo effects of octanoylated goldfish ghrelin peptides (gGRL-19 and gGRL-12) on luteinizing hormone (LH) and growth hormone (GH) release in goldfish. gGRL-19 and gGRL-12 at picomolar doses stimulated LH and GH release from dispersed goldfish pituitary cells in perifusion and static incubation. Incubation of pituitary cells for 2 h with 10 nM gGRL-12 and 1 or 10 nM gGRL-19 increased LH-β mRNA expression, whereas only 10 nM gGRL-19 increased GH mRNA expression. Somatostatin-14 abolished the stimulatory effects of ghrelin on GH release from dispersed pituitary cells in perifusion and static culture. The GH secretagogue receptor antagonist d-Lys3-GHRP-6 inhibited the ghrelin-induced LH release, whereas no effects were found on stimulation of GH release by ghrelin. Intracerebroventricular injection of 1 ng/g body wt of gGRL-19 or intraperitoneal injection of 100 ng/g body wt of gGRL-19 increased serum LH levels at 60 min after injection, whereas significant increases in GH levels were found at 15 and 30 min after these treatments. Our results indicate that, in addition to its potent stimulatory actions on GH release, goldfish ghrelin peptides have the novel function of stimulating LH release in goldfish.

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