A novel missense mutation in the mouse growth hormone gene causes semidominant dwarfism, hyperghrelinemia, and obesity.

Abstract:

:The SMA1-mouse is a novel ethyl-nitroso-urea (ENU)-induced mouse mutant that carries an a-->g missense mutation in exon 5 of the GH gene, which translates to a D167G amino acid exchange in the mature protein. Mice carrying the mutation are characterized by dwarfism, predominantly due to the reduction (sma1/+) or absence (sma1/sma1) of the GH-mediated peripubertal growth spurt, with sma1/+ mice displaying a less pronounced phenotype. All genotypes are viable and fertile, and the mode of inheritance is in accordance with a semidominant Mendelian trait. Adult SMA1 mice accumulate excessive amounts of sc and visceral fat in the presence of elevated plasma ghrelin levels, possibly reflecting altered energy partitioning. Our results suggest impaired storage and/or secretion of pituitary GH in mutants, resulting in reduced pituitary GH and reduced GH-stimulated IGF-1 expression. Generation and identification of the SMA1 mouse exemplifies the power of the combination of random mouse mutagenesis with a highly detailed phenotype-analysis as a successful strategy for the detection and analysis of novel gene-function relationships.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Meyer CW,Korthaus D,Jagla W,Cornali E,Grosse J,Fuchs H,Klingenspor M,Roemheld S,Tschöp M,Heldmaier G,De Angelis MH,Nehls M

doi

10.1210/en.2003-1125

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

2531-41

issue

5

eissn

0013-7227

issn

1945-7170

pii

en.2003-1125

journal_volume

145

pub_type

杂志文章
  • Involvement of postnatal gonads in the maturation of dopaminergic regulation of prolactin secretion in male rats.

    abstract::Permanent effects of postnatal gonads on dopamine (DA)-mediated regulation of PRL secretion were examined in adult male rats of the Wistar-Imamichi strain. Rats were bilaterally orchidectomized at varying postnatal days, i.e. 8 h after birth [neonatal castration (NC)] or at 1, 2, 3, 4, or 6 weeks of age, and subjected...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-120-6-2205

    authors: Watanobe H,Takebe K

    更新日期:1987-06-01 00:00:00

  • Effects of free fatty acids on luteinizing hormone and growth hormone secretion in ovariectomized lambs.

    abstract::The effects of FFA on circulating LH and GH concentrations in ovariectomized ewe lambs were investigated. Lambs (n = 14) were weaned at 2.5 months, ovariectomized at 6.5 months, and used at 8.5 months of age. From weaning until day 0 of the experiment, lambs were fed to maintain body weights (23 kg). On day 0, serum F...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-126-4-1934

    authors: Estienne MJ,Schillo KK,Hileman SM,Green MA,Hayes SH,Boling JA

    更新日期:1990-04-01 00:00:00

  • Medroxyprogesterone acetate antagonizes estrogen up-regulation of brain mitochondrial function.

    abstract::The impact of clinical progestins used in contraception and hormone therapies on the metabolic capacity of the brain has long-term implications for neurological health in pre- and postmenopausal women. Previous analyses indicated that progesterone and 17β-estradiol (E2) sustain and enhance brain mitochondrial energy-t...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2010-1061

    authors: Irwin RW,Yao J,Ahmed SS,Hamilton RT,Cadenas E,Brinton RD

    更新日期:2011-02-01 00:00:00

  • Decidual prolactin silences the expression of genes detrimental to pregnancy.

    abstract::Although the main role of prolactin (PRL) in pregnant rodents is to sustain progesterone production by the corpus luteum, progesterone treatment of PRL or PRL receptor (PRL-R) null mice is unable to prevent fetal loss. We have previously shown that the rat decidua is a site of PRL production and action. In this report...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2006-1643

    authors: Bao L,Tessier C,Prigent-Tessier A,Li F,Buzzio OL,Callegari EA,Horseman ND,Gibori G

    更新日期:2007-05-01 00:00:00

  • Regulation of rat granulosa cell differentiation by extracellular matrix produced by bovine corneal endothelial cells.

    abstract::The effect of bovine corneal extracellular matrix (ECM) on gonadotropin-primed rat granulosa cells in vitro was studied by examining the following parameters: 1) rate of cell attachment to culture dishes; 2) modulation of cell morphology; 3) specific binding of [125I]human(h)CG to LH/hCG receptors; 4) cAMP response to...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-118-5-1878

    authors: Furman A,Rotmensch S,Kohen F,Mashiach S,Amsterdam A

    更新日期:1986-05-01 00:00:00

  • Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus.

    abstract::Prolonged fasting is associated with a number of changes in the thyroid axis manifested by low serum T3 and T4 levels and, paradoxically, low or normal TSH. This response is, at least partly, caused by suppression of proTRH gene expression in neurons of the hypothalamic paraventricular nucleus (PVN) and reduced hypoth...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.138.6.5209

    authors: Légrádi G,Emerson CH,Ahima RS,Flier JS,Lechan RM

    更新日期:1997-06-01 00:00:00

  • Disparate changes in kisspeptin and neurokinin B expression in the arcuate nucleus after sex steroid manipulation reveal differential regulation of the two KNDy peptides in rats.

    abstract::Kisspeptin, neurokinin B (NKB) and dynorphin A are coexpressed in a population of neurons in the arcuate nucleus (ARC), termed KNDy neurons, which were recently recognized as important elements for the generation of GnRH pulses. However, the topographic distribution of these peptides and their regulated expression by ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2014-1200

    authors: Overgaard A,Ruiz-Pino F,Castellano JM,Tena-Sempere M,Mikkelsen JD

    更新日期:2014-10-01 00:00:00

  • Inhibitory effects of retinoic acids on androgen-dependent development of neonatal mouse seminal vesicles in vitro.

    abstract::The effects of retinoic acids (RAs) on development of seminal vesicles (SVs) of neonatal mice were investigated in vitro. SVs from 0-day-old male mice were cultured for 2-6 days in serum-free, chemically defined medium containing transferrin and BSA supplemented with 5alpha-dihydrotestosterone (DHT; 10(-8) M) and insu...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.137.7.8770910

    authors: Tanji N,Yokoyama M,Takeuchi M,Terada N,Dahiya R,Cunha GR

    更新日期:1996-07-01 00:00:00

  • Tumor necrosis factor-alpha attenuation of luteinizing hormone-stimulated androstenedione production by ovarian theca-interstitial cells: inhibition at loci within the adenosine 3',5'-monophosphate-dependent signaling pathway.

    abstract::Tumor necrosis factor-alpha (TNF) blocks LH-stimulated androstenedione production by immature rat theca-interstitial cells (TIC) in vitro. The mechanism for TNF inhibition of LH-induced androstenedione is unknown and was investigated. LH stimulation of androstenedione synthesis in TIC is mediated via a cAMP-dependent ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.133.5.8404680

    authors: Zachow RJ,Tash JS,Terranova PF

    更新日期:1993-11-01 00:00:00

  • Attenuation by a 5 alpha-reductase inhibitor of the activational effect of testosterone propionate on penile erections in castrated male rats.

    abstract::Daily administration of an inhibitor of 5 alpha-reductase, 17 beta-testosterone carboxylic acid, significantly attenuated the stimulatory effect of testosterone propionate on penile erections displayed by castrated male rats which were restrained in a supine position. This treatment, however, failed to affect mating b...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-109-4-1047

    authors: Bradshaw WG,Baum MJ,Awh CC

    更新日期:1981-10-01 00:00:00

  • Expression of steroidogenic enzymes in the bovine placenta and fetal adrenal glands throughout gestation.

    abstract::The expression of cholesterol side-chain cleavage cytochrome P450 (P450scc), 17 alpha-hydroxylase cytochrome P450 (P45017 alpha), and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) was studied in bovine placenta and fetal adrenal glands throughout gestation. The levels of expression of these enzymes were much lower ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.130.5.1374010

    authors: Conley AJ,Head JR,Stirling DT,Mason JI

    更新日期:1992-05-01 00:00:00

  • Discordant effects of aging on prolactin and luteinizing hormone-beta messenger ribonucleic acid levels in the female rat.

    abstract::To examine the molecular genetic basis for the age-related increase in PRL secretion and decrease in LH production in the rat, we measured steady state levels of PRL and LH beta mRNA in pituitary homogenates and cell lysates from monolayer adenohypophyseal cultures. These mRNA levels were compared with the correspondi...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-126-2-773

    authors: Stewart DA,Blackman MR,Kowatch MA,Danner DB,Roth GS

    更新日期:1990-02-01 00:00:00

  • Methylamine and monensin do not block insulin internalization but do influence the intracellular distribution and action of insulin in pancreatic acini from diabetic mice.

    abstract::Methylamine and monensin are two agents known to interfere with the recycling of membrane receptors. In the present investigation, we studied their effects on the binding, intracellular distribution, and action of insulin in isolated pancreatic acini prepared from diabetic mice. These drugs had several similar effects...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-115-1-205

    authors: Potau N,Bailey AC,Roach E,Williams JA,Goldfine ID

    更新日期:1984-07-01 00:00:00

  • Melatonin stimulates the release of growth hormone and prolactin by a possible induction of the expression of frog growth hormone-releasing peptide and its related peptide-2 in the amphibian hypothalamus.

    abstract::We recently identified a novel hypothalamic neuropeptide stimulating GH release in bullfrogs and termed it frog GH-releasing peptide (fGRP). The fGRP precursor encodes fGRP and its related peptides (fGRP-RP-1, -RP-2, and -RP-3), and fGRP-RP-2 also stimulates GH and prolactin (PRL) release. Cell bodies and terminals co...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2007-1427

    authors: Chowdhury VS,Yamamoto K,Saeki I,Hasunuma I,Shimura T,Tsutsui K

    更新日期:2008-03-01 00:00:00

  • Ovarian vitamin E accumulation: evidence for a role of lipoproteins.

    abstract::Reactive oxygen species, such as superoxide, hydrogen peroxide, and lipid peroxides, impair luteal function. Vitamin E, a lipophilic antioxidant vitamin, provides a major avenue of protection by scavenging free radicals and terminating lipid peroxidation. We previously showed that ovarian vitamin E levels increase aft...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.135.2.8033800

    authors: Aten RF,Kolodecik TR,Behrman HR

    更新日期:1994-08-01 00:00:00

  • Veratridine and ouabain stimulate calcium-dependent prolactin release.

    abstract::We have investigated the effects of veratridine, a Na+ channel activator, and ouabain, an inhibitor of Na+-K+-ATPase, on short term (1-h) PRL release from primary cultures of rat anterior pituitary cells and from the rat anterior pituitary cell line GH4C1 in culture. Both compounds should increase intracellular Na+. V...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-113-4-1228

    authors: Scammell JG,Dannies PS

    更新日期:1983-10-01 00:00:00

  • Dopamine inhibits inositol phosphate production, arachidonic acid formation, and corticosteroid release by frog adrenal gland through a pertussis toxin-sensitive G-protein.

    abstract::We have previously shown that dopamine-evoked inhibition of corticosteroid production from adrenocortical cells is mediated through a decrease in prostaglandin biosynthesis. Since the catecholamine did not alter the stimulatory effect of arachidonic acid, it was proposed that dopamine may inhibit the formation of arac...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-128-5-2625

    authors: Morra M,Leboulenger F,Desrues L,Tonon MC,Vaudry H

    更新日期:1991-05-01 00:00:00

  • Implications of progesterone metabolism in MA-10 cells for accurate measurement of the rate of steroidogenesis.

    abstract::In virtually all studies with MA-10 cells, progesterone RIAs have been used to measure steroid synthesis. To test whether progesterone is a stable end product, we investigated the metabolism of added tritiated progesterone and pregnenolone in MA-10 cells over a period of 3 h. Steroids were then extracted, separated by...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.142.12.8545

    authors: Rommerts FF,King SR,Span PN

    更新日期:2001-12-01 00:00:00

  • Lateral Hypothalamic Area Neurotensin Neurons Are Required for Control of Orexin Neurons and Energy Balance.

    abstract::The lateral hypothalamic area (LHA) is essential for motivated ingestive and locomotor behaviors that impact body weight, yet it remains unclear how the neurochemically defined subpopulations of LHA neurons contribute to energy balance. In particular, the role of the large population of LHA neurotensin (Nts) neurons h...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2018-00311

    authors: Brown J,Sagante A,Mayer T,Wright A,Bugescu R,Fuller PM,Leinninger G

    更新日期:2018-09-01 00:00:00

  • Prolactin restores plasma testosterone levels and stimulates testicular growth in hamsters exposed to short day-length.

    abstract::In male hamsters, light deprivation was reported to reduce both testis weight and prolactin (PRL) levels. Therefore, we decided to examine the effects of PRL on testicular function in hamsters exposed to short day-length. Adult hamsters were exposed to 5 h of light per day to induce gonadal atrophy, and, starting two ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:

    authors: Bartke A,Croft BT,Dalterio S

    更新日期:1975-12-01 00:00:00

  • Regulation of the hypothalamic-pituitary-adrenal axis circadian rhythm by endocannabinoids is sexually diergic.

    abstract::We have examined the effects of acute administration of the cannabinoid receptor type 1 (CB(1)) antagonist AM251 on the rat hypothalamic-pituitary-adrenal (HPA) axis with respect to both gender and time of day. Blood samples were collected from conscious male and female rats every 5 min using an automated blood sampli...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2010-0101

    authors: Atkinson HC,Leggett JD,Wood SA,Castrique ES,Kershaw YM,Lightman SL

    更新日期:2010-08-01 00:00:00

  • The immature rat ovary is innervated by vasoactive intestinal peptide (VIP)-containing fibers and responds to VIP with steroid secretion.

    abstract::The nature and role of the peptidergic innervation of the ovary were examined by determining the location and function of vasoactive intestinal peptide (VIP)-containing nerve fibers in the immature rat ovary. Immunohistofluorescence analysis of prepubertal ovaries using a specific VIP antibody revealed sparse delicate...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-118-4-1682

    authors: Ahmed CE,Dees WL,Ojeda SR

    更新日期:1986-04-01 00:00:00

  • Dynamic regulation of RGS2 in bone: potential new insights into parathyroid hormone signaling mechanisms.

    abstract::The initial steps involved in mediating the transduction of PTH signal via its G protein-coupled receptors are well understood and occur through the activation of cAMP and phospholipase C pathways. However, the cellular and molecular mechanisms for subsequent receptor desensitization are less well understood. Recently...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.141.1.7229

    authors: Miles RR,Sluka JP,Santerre RF,Hale LV,Bloem L,Boguslawski G,Thirunavukkarasu K,Hock JM,Onyia JE

    更新日期:2000-01-01 00:00:00

  • Identification and distribution of a novel platelet-derived growth factor receptor beta variant: effect of retinoic acid and involvement in cell differentiation.

    abstract::We have shown previously that neonatal testicular gonocytes express platelet-derived growth factor receptors (PDGFR) alpha and beta. We report the expression of a novel PDGFRbeta (V1-PDGFRbeta) transcript in gonocytes of 3-d-old rat testes. V1-PDGFRbeta nucleotide sequence spans from intron 6 to exon 23 of the PDGFRbe...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2006-1206

    authors: Wang Y,Culty M

    更新日期:2007-05-01 00:00:00

  • Marked seasonal changes in response to the negative feedback action of estradiol on luteinizing hormone secretion in the female Japanese monkey.

    abstract::The seasonal changes in response to the negative feedback action of estradiol on LH secretion were studied in two groups of ovariectomized Japanese monkeys (Macaca fuscata fuscata; n = 6). Blood samples were collected two to three times a week, and changes in serum concentrations of LH, estradiol, and progesterone wer...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-128-3-1291

    authors: Nozaki M,Watanabe G,Taya K

    更新日期:1991-03-01 00:00:00

  • Mechanisms involved in glucocorticoid induction of pituitary GH expression during embryonic development.

    abstract::Glucocorticoid hormones are involved in functional differentiation of GH-producing somatotrophs. Glucocorticoid treatment prematurely induces GH expression in mammals and birds in a process requiring protein synthesis and Rat sarcoma (Ras) signaling. The objective of this study was to investigate mechanisms through wh...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2014-1686

    authors: Ellestad LE,Puckett SA,Porter TE

    更新日期:2015-03-01 00:00:00

  • Annexin 1 (lipocortin 1) mediates the glucocorticoid inhibition of cyclic adenosine 3',5'-monophosphate-stimulated prolactin secretion.

    abstract::Our previous studies have identified a role for annexin 1 (also called lipocortin 1) in the regulatory actions of glucocorticoids (GCs) on the release of PRL from the rat anterior pituitary gland. In the present study we used antisense and immunoneutralization strategies to extend this work. Exposure of rat anterior p...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.141.6.7512

    authors: Taylor AD,Philip JG,John CD,Cover PO,Morris JF,Flower RJ,Buckingham JC

    更新日期:2000-06-01 00:00:00

  • Novel self-regulation of human chorionic gonadotropin biosynthesis in term pregnancy human placenta.

    abstract::Term pregnancy human placenta contains hCG/LH receptor mRNA transcripts and immunoreactive receptor protein. Both the receptor transcripts and receptor proteins are present only in trophoblasts. These findings led us to investigate whether hCG can regulate its own synthesis in term pregnancy human placenta. Treatment ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.133.6.8243330

    authors: Licht P,Cao H,Lei ZM,Rao CV,Merz WE

    更新日期:1993-12-01 00:00:00

  • Immunocytochemical distribution of aromatase cytochrome P450 in the rat brain using peptide-generated polyclonal antibodies.

    abstract::Estrogen formation is catalyzed by the aromatase cytochrome P450 (P450AROM) enzyme. Aromatase activity has been detected in several regions in the rat brain. In the present study, we used peptide-generated polyclonal antibodies raised against a 20-amino acid synthetic fragment of the rat P450AROM protein (as deduced f...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-129-6-2834

    authors: Sanghera MK,Simpson ER,McPhaul MJ,Kozlowski G,Conley AJ,Lephart ED

    更新日期:1991-12-01 00:00:00

  • β2-Adrenergic receptor signaling in osteoblasts contributes to the catabolic effect of glucocorticoids on bone.

    abstract::The sympathetic nervous system is a physiological regulator of bone homeostasis. Autonomic nerves are indeed present in bone, bone cells express the β2-adrenergic receptors (β2AR), and pharmacological or genetic disruption of sympathetic outflow to bone induces bone gain in rodents. These recent findings implied that ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2010-0881

    authors: Ma Y,Nyman JS,Tao H,Moss HH,Yang X,Elefteriou F

    更新日期:2011-04-01 00:00:00