DOCSLIB.ORG

Adrenocorticosteroids Chapter 19

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Adrenocorticosteroids Chapter 19 ADRENOCORTICOSTEROIDS CHAPTER 19 Adrenocorticosteroids = group of agents secreted by the adrenal cortex Dental uses Medical Uses Mechanism of release stress → hypothalamus releases CRF → pituitary releases ACTH → adrenal cortex releases hydrocortisone . Classification of Steroids glucocorticoids mineralcorticoids Disease States Addison’s disease Cushing’s syndrome Mechanism of Action steroid binds to receptor → forms steroid-receptor complex → complex enters nucleus, turns genes on/off anti-inflammatory Pharmacologic effects - palliative (not curative) glucocorticoids prednisone, methylprednisolone, triamcinolone 1. anti-inflammatory 2. suppress allergic reactions 3. suppress immune response mineralcorticoids 1. ↑ Na+ retention 2. ↑ K+ loss 3. ↑ edema, hypertension ADR’s Glucocorticooids (see fig 19-2, pg 243) 1. metabolic changes - look like Cushing’s syndrome (see fig. 19-3, pg 244) 2. infections - because of anti-inflammatory action 3. CNS - changes in personality and behavior (euphoria with high dose, depression with lower dose) 4. peptic ulcer - corticosteroids stimulate stomach acid 5. impaired wound healing / osteoporosis - impaired synthesis of collagen 6. ophthalmic effects - increased intraoccular pressure 7. electrolyte / fluid balance - can have some mineralcorticoid action 8. adrenal crisis - adrenal gland atrophies with prolonged use; can be lethal 9. dental effects a. slow healing of mucosal surfaces b. oral candidiasis with steroid inhalers (asthma) Medical Uses 1. Addison’s disease 2. Cushing’s syndrome (Rx, adrenal tumor, pituitary tumor) 3. autoimmune diseases a. rheumatoid arthritis b. collagen diseases 4. with chemotherapy in CA tx (anti-emetic/anti-nausea, and to reduce swelling which decreases pain) 5. asthma 6. emergencies - tx shock, tx adrenal crisis 7. tx inflammatory and allergic reactions (palliative only, not curative) (most common) Dental Uses 1. oral lesions - tx of noninfectious inflammatory diseases (most common) RAS 2. oral surgery - ↓ post-op edema, trismus, and pain (?) 3. pulp procedures (?) Dental Implications 1. GI - stimulate stomach acid, avoid Rx Salicylates (ASA) and NSAID’s 2. check BP - can exacerbate hypertension 3. glaucoma - avoid Rx anticholinergics 4. be aware of possible behavior changes 5. osteoporosis 6. infection - infection symptoms may be masked, pt. has decreased ability to fight infection 7. delayed wound healing - special care in suturing 8. adrenal crisis - only with severe stress 9. periodontal disease - interfere with body’s response to infection, osteoporosis Steroid supplementation most dental patients taking steroids having normal dental tx rendered DO NOT need additional steroids (see fig 19-4, pg 247) OTHER HORMONES CHAPTER 20 Hormones Pituitary Hormones (pituitary = “master gland”, hypophysis) Anterior (adenohypophysis) 1. GH growth hormone (somatotropin) gigantism acromegaly dwarfism 2. LH leutinizing hormone 3. FSH follicle stimulating hormone 4. TSH thyroid stimulating hormone (thyrotropin) 5. ACTH adrenocorticotropic hormone 6. PRL prolactin (leuteotropic hormone LTH) 7. β - lipotropin Posterior (neurohypophysis) 1. Vasopressin (antidiuretic hormone - ADH) 2. Oxytocin Thyroid Hormones Iodine-containing 1. T3 (tri-iodo-thyronine) 2. T4 (thyroxine) Hypothyroid child: cretinism adult: myxedema Hyperthyroid thyrotoxicosis Grave’s disease Plummer’s disease Hashimoto’s disease Calcitonin Pancreatic Hormones Insulin Glucagon Diabetes mellitus: def. abnormal carbohydrate metabolism with inappropriate hyperglycemia Type I (IDDM, juvenile onset) Type II (NIDDM, adult onset) Systemic complications Oral complications Management of DM patient Evaluation Medical emergencies Hypoglycemia Hyperglycemia Drugs used to manage diabetes (add’l resource: http://en.wikipedia.org/wiki/Anti-diabetic_medication) Type I Insulin: Lantus, Humalog, Humulin N, Humulin 70/30, Novolog Mix 70/30, Novolin 70/30 Type II Sulfonylureas: glimepiride, glyburide, glipizide (secretagogues) MA: ↑ release of insulin from beta cells, ↓ serum glucagon, ↑ insulin sensitivity in target tissues ADR’s: blood dyscrasias, GI, cutaneous, liver damage meglitinide derivatives (non-sulfonylurea secretagogues): repaglinide (Prandin) nateglinide (Starlix) MA: ↑ release of insulin from beta cells, ADR’s: must be taken with meals Biguanides: metformin MA: ↓ hepatic production of glucose, ↑ insulin sensitivity in target tissues ADR’s: GI, lactic acidosis thiazolidinediones (glitazones): Actos, Avandia MA: ↑ insulin sensitivity in target tissues ADR’s: weight gain, hepatotoxicity new drugs exenatide (Byetta) (secretagogue, incretin mimetic, glucagon-like peptide / GLP-1) MA: ↑ release of insulin from beta cells, ↓ serum glucagon, ↑ satiety ADR’s: GI, risk of hypoglycemia when used with other oral diabetic agents pramlintide (Symlin) (amylin analog) MA: modulation gastric emptying, prevent postprandial rise in plasma glucagon, ↑ satiety Amylin secreted along with insulin by pancreatic β- cells ADR’s: GI, risk of hypoglycemia when used with other oral diabetic agents DPP-4 inhibitors (Januvia / sitaglipton) MA: ↑insulin synthesis, oppose glucagon ADR’s: weight gain when used with sulfonylurea α-glucosidase inhibitors ( acarbose) MA: delay/prevent digestion of ingested carbohydrate (small intestine), delays glucose adsorption ADR’s: flatulence, GI Female Sex Hormones Estrogens: Premirin, Evista, Estradiol Progestins Oral contraceptives: NuvaRing, Loestrin 24 Fe Management of patient taking oral contraceptives: Drug interactions: Male Sex Hormones (testosterone) Other Agents clomiphene leuprolide tamoxifen danazol aromatase inhibitors .
Load more

Recommended publications
  • Searching for Novel Peptide Hormones in the Human Genome Olivier Mirabeau
    Searching for novel peptide hormones in the human genome Olivier Mirabeau To cite this version: Olivier Mirabeau. Searching for novel peptide hormones in the human genome. Life Sciences [q-bio]. Université Montpellier II - Sciences et Techniques du Languedoc, 2008. English. tel-00340710 HAL Id: tel-00340710 https://tel.archives-ouvertes.fr/tel-00340710 Submitted on 21 Nov 2008 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITE MONTPELLIER II SCIENCES ET TECHNIQUES DU LANGUEDOC THESE pour obtenir le grade de DOCTEUR DE L'UNIVERSITE MONTPELLIER II Discipline : Biologie Informatique Ecole Doctorale : Sciences chimiques et biologiques pour la santé Formation doctorale : Biologie-Santé Recherche de nouvelles hormones peptidiques codées par le génome humain par Olivier Mirabeau présentée et soutenue publiquement le 30 janvier 2008 JURY M. Hubert Vaudry Rapporteur M. Jean-Philippe Vert Rapporteur Mme Nadia Rosenthal Examinatrice M. Jean Martinez Président M. Olivier Gascuel Directeur M. Cornelius Gross Examinateur Résumé Résumé Cette thèse porte sur la découverte de gènes humains non caractérisés codant pour des précurseurs à hormones peptidiques. Les hormones peptidiques (PH) ont un rôle important dans la plupart des processus physiologiques du corps humain.
    [Show full text]
  • Effects of Β-Lipotropin and Β-Lipotropin-Derived Peptides on Aldosterone Production in the Rat Adrenal Gland
    Effects of β-Lipotropin and β-Lipotropin-derived Peptides on Aldosterone Production in the Rat Adrenal Gland Hiroaki Matsuoka, … , Patrick J. Mulrow, Roberto Franco-Saenz J Clin Invest. 1981;68(3):752-759. https://doi.org/10.1172/JCI110311. Research Article To investigate the role of non-ACTH pituitary peptides on steroidogenesis, we studied the effects of synthetic β-lipotropin, β-melanotropin, and β-endorphin on aldosterone and corticosterone stimulation using rat adrenal collagenase-dispersed capsular and decapsular cells. β-lipotropin induced a significant aldosterone stimulation in a dose-dependent fashion (10 nM-1 μM). β-endorphin, which is the carboxyterminal fragment of β-lipotropin, did not stimulate aldosterone production at the doses used (3 nM-6 μM). β-melanotropin, which is the middle fragment of β-lipotropin, showed comparable effects on aldosterone stimulation. β-lipotropin and β-melanotropin did not affect corticosterone production in decapsular cells. Although ACTH1-24 caused a significant increase in cyclic AMP production in capsular cells in a dose-dependent fashion (1 nM-1 μM), β-lipotropin and β-melanotropin did not induce an increase in cyclic AMP production at the doses used (1 nM-1 μM). The β-melanotropin analogue (glycine[Gly]10-β-melanotropin) inhibited aldosterone production induced by β- lipotropin or β-melanotropin, but did not inhibit aldosterone production induced by ACTH1-24 or angiotensin II. Corticotropin-inhibiting peptide (ACTH7-38) inhibited not only ACTH1-24 action but also β-lipotropin or β-melanotropin action; however it did not affect angiotensin II-induced aldosterone production. (saralasin [Sar]1; alanine [Ala]8)- Angiotensin II inhibited the actions of β-lipotropin and β-melanotropin as well as angiotensin II.
    [Show full text]
  • Lipotropin, Melanotropin and Endorphin: in Vivo Catabolism and Entry Into Cerebrospinal Fluid
    LE JOURNAL CANAD1EN DES SCIENCES NEUROLOGIQUES Lipotropin, Melanotropin and Endorphin: In Vivo Catabolism and Entry into Cerebrospinal Fluid P. D. PEZALLA, M. LIS, N. G. SEIDAH AND M. CHRETIEN SUMMARY: Anesthetized rabbits were INTRODUCTION (Rudman et al., 1974). These findings given intravenous injections of either Beta-lipotropin (beta-LPH) is a suggest, albeit weakly, that the pep­ beta-lipotropin (beta-LPH), beta- peptide of 91 amino acids that was tide might cross the blood-brain bar­ melanotropin (beta-MSH) or beta- first isolated from ovine pituitary rier. In the case of beta-endorphin, endorphin. The postinjection concentra­ glands (Li et al., 1965). Although there are physiological studies both tions of these peptides in plasma and cerebrospinal fluid (CSF) were measured beta-LPH has a number of physiologi­ supporting and negating the possibil­ by radioimmunoassay (RIA). The plasma cal actions including the stimulation ity that beta-endorphin crosses the disappearance half-times were 13.7 min of lipolysis and melanophore disper­ blood-brain barrier. The study of for beta-LPH, 5.1 min for beta-MSH, and sion, it is believed to function princi­ Tseng et al. (1976) supports this pos­ 4.8 min for beta-endorphin. Circulating pally as a prohormone for beta- sibility since they observed analgesia beta-LPH is cleaved to peptides tenta­ melanotropin (beta-MSH) and beta- in mice following intravenous injec­ tively identified as gamma-LPH and endorphin. Beta-MSH, which com­ tion of beta-endorphin. However, beta-endorphin. Each of these peptides prises the sequence 41-58 of beta- Pert et al. (1976) were unable to elicit appeared in the CSF within 2 min postin­ LPH, is considerably more potent central effects in rats by intravenous jection.
    [Show full text]
  • I AMYLIN MEDIATES BRAINSTEM
    AMYLIN MEDIATES BRAINSTEM CONTROL OF HEART RATE IN THE DIVING REFLEX A Dissertation Submitted to The Temple University Graduate Board In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy By Fan Yang May, 2012 Examination committee members: Dr. Nae J Dun (advisor), Dept. of Pharmacology, Temple University Dr. Alan Cowan, Dept. of Pharmacology, Temple University Dr. Lee-Yuan Liu-Chen, Dept. of Pharmacology, Temple University Dr. Gabriela Cristina Brailoiu, Dept. of Pharmacology, Temple University Dr. Parkson Lee-Gau Chong, Dept. of Biochemistry, Temple University Dr. Hreday Sapru (external examiner), Depts. of Neurosciences, Neurosurgery & Pharmacology/Physiology, UMDNJ-NJMS. i © 2012 By Fan Yang All Rights Reserved ii ABSTRACT AMYLIN’S ROLE AS A NEUROPEPTIDE IN THE BRAINSTEM Fan Yang Doctor of Philosophy Temple University, 2012 Doctoral Advisory Committee Chair: Nae J Dun, Ph.D. Amylin, or islet amyloid polypeptide is a 37-amino acid member of the calcitonin peptide family. Amylin role in the brainstem and its function in regulating heart rates is unknown. The diving reflex is a powerful autonomic reflex, however no neuropeptides have been described to modulate its function. In this thesis study, amylin expression in the brainstem involving pathways between the trigeminal ganglion and the nucleus ambiguus was visualized and characterized using immunohistochemistry. Its functional role in slowing heart rate and also its involvement in the diving reflex were elucidated using stereotaxic microinjection, whole-cel patch-clamp, and a rat diving model. Immunohistochemical and tract tracing studies in rats revealed amylin expression in trigeminal ganglion cells, which also contained vesicular glutamate transporter 2 positive.
    [Show full text]
  • A 0.70% E 0.80% Is 0.90%
    US 20080317666A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0317666 A1 Fattal et al. (43) Pub. Date: Dec. 25, 2008 (54) COLONIC DELIVERY OF ACTIVE AGENTS Publication Classification (51) Int. Cl. (76) Inventors: Elias Fattal, Paris (FR); Antoine A6IR 9/00 (2006.01) Andremont, Malakoff (FR); A61R 49/00 (2006.01) Patrick Couvreur, A6II 5L/12 (2006.01) Villebon-sur-Yvette (FR); Sandrine A6IPI/00 (2006.01) Bourgeois, Lyon (FR) (52) U.S. Cl. .......................... 424/1.11; 424/423; 424/9.1 (57) ABSTRACT Correspondence Address: Drug delivery devices that are orally administered, and that David S. Bradlin release active ingredients in the colon, are disclosed. In one Womble Carlyle Sandridge & Rice embodiment, the active ingredients are those that inactivate P.O.BOX 7037 antibiotics, such as macrollides, quinolones and beta-lactam Atlanta, GA 30359-0037 (US) containing antibiotics. One example of a Suitable active agent is an enzyme Such as beta-lactamases. In another embodi ment, the active agents are those that specifically treat colonic (21) Appl. No.: 11/628,832 disorders, such as Chrohn's Disease, irritable bowel syn drome, ulcerative colitis, colorectal cancer or constipation. (22) PCT Filed: Feb. 9, 2006 The drug delivery devices are in the form of beads of pectin, crosslinked with calcium and reticulated with polyethylene imine. The high crosslink density of the polyethyleneimine is (86). PCT No.: PCT/GBO6/OO448 believed to stabilize the pectin beads for a sufficient amount of time such that a Substantial amount of the active ingredi S371 (c)(1), ents can be administered directly to the colon.
    [Show full text]
  • Evolution of the Neuropeptide Y and Opioid Systems and Their Genomic
    It's time to try Defying gravity I think I'll try Defying gravity And you can't pull me down Wicked List of Papers This thesis is based on the following papers, which are referred to in the text by their Roman numerals. I Sundström G, Larsson TA, Brenner S, Venkatesh B, Larham- mar D. (2008) Evolution of the neuropeptide Y family: new genes by chromosome duplications in early vertebrates and in teleost fishes. General and Comparative Endocrinology Feb 1;155(3):705-16. II Sundström G, Larsson TA, Xu B, Heldin J, Lundell I, Lar- hammar D. (2010) Interactions of zebrafish peptide YYb with the neuropeptide Y-family receptors Y4, Y7, Y8a and Y8b. Manuscript III Sundström G, Xu B, Larsson TA, Heldin J, Bergqvist CA, Fredriksson R, Conlon JM, Lundell I, Denver RJ, Larhammar D. (2010) Characterization of the neuropeptide Y system's three peptides and six receptors in the frog Silurana tropicalis. Manu- script IV Dreborg S, Sundström G, Larsson TA, Larhammar D. (2008) Evolution of vertebrate opioid receptors. Proc Natl Acad Sci USA Oct 7;105(40):15487-92. V Sundström G, Dreborg S, Larhammar D. (2010) Concomitant duplications of opioid peptide and receptor genes before the origin of jawed vertebrates. PLoS One May 6;5(5):e10512. VI Sundström G, Larsson TA, Larhammar D. (2008) Phylogenet- ic and chromosomal analyses of multiple gene families syntenic with vertebrate Hox clusters. BMC Evolutionary Biology Sep 19;8:254. VII Widmark J, Sundström G, Ocampo Daza D, Larhammar D. (2010) Differential evolution of voltage-gated sodium channels in tetrapods and teleost fishes.
    [Show full text]
  • Five Decades of Research on Opioid Peptides: Current Knowledge and Unanswered Questions
    Molecular Pharmacology Fast Forward. Published on June 2, 2020 as DOI: 10.1124/mol.120.119388 This article has not been copyedited and formatted. The final version may differ from this version. File name: Opioid peptides v45 Date: 5/28/20 Review for Mol Pharm Special Issue celebrating 50 years of INRC Five decades of research on opioid peptides: Current knowledge and unanswered questions Lloyd D. Fricker1, Elyssa B. Margolis2, Ivone Gomes3, Lakshmi A. Devi3 1Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; E-mail: [email protected] 2Department of Neurology, UCSF Weill Institute for Neurosciences, 675 Nelson Rising Lane, San Francisco, CA 94143, USA; E-mail: [email protected] 3Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, Annenberg Downloaded from Building, One Gustave L. Levy Place, New York, NY 10029, USA; E-mail: [email protected] Running Title: Opioid peptides molpharm.aspetjournals.org Contact info for corresponding author(s): Lloyd Fricker, Ph.D. Department of Molecular Pharmacology Albert Einstein College of Medicine 1300 Morris Park Ave Bronx, NY 10461 Office: 718-430-4225 FAX: 718-430-8922 at ASPET Journals on October 1, 2021 Email: [email protected] Footnotes: The writing of the manuscript was funded in part by NIH grants DA008863 and NS026880 (to LAD) and AA026609 (to EBM). List of nonstandard abbreviations: ACTH Adrenocorticotrophic hormone AgRP Agouti-related peptide (AgRP) α-MSH Alpha-melanocyte stimulating hormone CART Cocaine- and amphetamine-regulated transcript CLIP Corticotropin-like intermediate lobe peptide DAMGO D-Ala2, N-MePhe4, Gly-ol]-enkephalin DOR Delta opioid receptor DPDPE [D-Pen2,D- Pen5]-enkephalin KOR Kappa opioid receptor MOR Mu opioid receptor PDYN Prodynorphin PENK Proenkephalin PET Positron-emission tomography PNOC Pronociceptin POMC Proopiomelanocortin 1 Molecular Pharmacology Fast Forward.
    [Show full text]
  • Anorexia Nervosa: a Unified Neurological Perspective Tasneem Fatema Hasan, Hunaid Hasan 
    Int. J. Med. Sci. 2011, 8 679 Ivyspring International Publisher International Journal of Medical Sciences 2011; 8(8):679-703 Review Anorexia Nervosa: A Unified Neurological Perspective Tasneem Fatema Hasan, Hunaid Hasan Mahatma Gandhi Mission’s Medical College, Aurangabad, Maharashtra, India Corresponding author: [email protected] or [email protected]. 1345 Daniel Creek Road, Mississau- ga, Ontario, L5V1V3, Canada. © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/ licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2011.05.03; Accepted: 2011.09.19; Published: 2011.10.22 Abstract The roles of corticotrophin-releasing factor (CRF), opioid peptides, leptin and ghrelin in anorexia nervosa (AN) were discussed in this paper. CRF is the key mediator of the hypo- thalamo-pituitary-adrenal (HPA) axis and also acts at various other parts of the brain, such as the limbic system and the peripheral nervous system. CRF action is mediated through the CRF1 and CRF2 receptors, with both HPA axis-dependent and HPA axis-independent ac- tions, where the latter shows nil involvement of the autonomic nervous system. CRF1 re- ceptors mediate both the HPA axis-dependent and independent pathways through CRF, while the CRF2 receptors exclusively mediate the HPA axis-independent pathways through uro- cortin. Opioid peptides are involved in the adaptation and regulation of energy intake and utilization through reward-related behavior. Opioids play a role in the addictive component of AN, as described by the “auto-addiction opioids theory”.
    [Show full text]
  • Lipotropin, Melanotropin and Endorphin: in Vivo Catabolism and Entry Into Cerebrospinal Fluid
    LE JOURNAL CANAD1EN DES SCIENCES NEUROLOGIQUES Lipotropin, Melanotropin and Endorphin: In Vivo Catabolism and Entry into Cerebrospinal Fluid P. D. PEZALLA, M. LIS, N. G. SEIDAH AND M. CHRETIEN SUMMARY: Anesthetized rabbits were INTRODUCTION (Rudman et al., 1974). These findings given intravenous injections of either Beta-lipotropin (beta-LPH) is a suggest, albeit weakly, that the pep­ beta-lipotropin (beta-LPH), beta- peptide of 91 amino acids that was tide might cross the blood-brain bar­ melanotropin (beta-MSH) or beta- first isolated from ovine pituitary rier. In the case of beta-endorphin, endorphin. The postinjection concentra­ glands (Li et al., 1965). Although there are physiological studies both tions of these peptides in plasma and cerebrospinal fluid (CSF) were measured beta-LPH has a number of physiologi­ supporting and negating the possibil­ by radioimmunoassay (RIA). The plasma cal actions including the stimulation ity that beta-endorphin crosses the disappearance half-times were 13.7 min of lipolysis and melanophore disper­ blood-brain barrier. The study of for beta-LPH, 5.1 min for beta-MSH, and sion, it is believed to function princi­ Tseng et al. (1976) supports this pos­ 4.8 min for beta-endorphin. Circulating pally as a prohormone for beta- sibility since they observed analgesia beta-LPH is cleaved to peptides tenta­ melanotropin (beta-MSH) and beta- in mice following intravenous injec­ tively identified as gamma-LPH and endorphin. Beta-MSH, which com­ tion of beta-endorphin. However, beta-endorphin. Each of these peptides prises the sequence 41-58 of beta- Pert et al. (1976) were unable to elicit appeared in the CSF within 2 min postin­ LPH, is considerably more potent central effects in rats by intravenous jection.
    [Show full text]
  • Direct Effects of Thyrotropin-Releasing Hormone, Cyproheptadine, and Dopamine on Adrenocorticotropin Secretion from Human Corticotroph Adenoma Cells in Vitro
    Direct effects of thyrotropin-releasing hormone, cyproheptadine, and dopamine on adrenocorticotropin secretion from human corticotroph adenoma cells in vitro. M Ishibashi, T Yamaji J Clin Invest. 1981;68(4):1018-1027. https://doi.org/10.1172/JCI110324. Research Article In an attempt to delineate the mechanism and the site of action of cyproheptadine and dopaminergic agonists as well as hormones including thyrotropin-releasing hormone (TRH) and hydrocortisone, the effects of these substances on ACTH secretion from corticotroph adenoma cells in culture were examined. Dispersed cells of pituitary adenomas obtained at surgery from four patients with Nelson's syndrome and one subject with Cushing's disease formed a monolayer and actively secreted ACTH into the medium. When TRH (0.1 microM) was added to the medium, a significant increase in ACTH secretion was demonstrated by adenoma cells from two patients who responded to TRH preoperatively. Moreover, a dose-response relationship between TRH concentrations and ACTH secretion was observed. Incubation of cells with cyproheptadine (1 or 0.1 microM) resulted in a significant decrease in ACTH release, and inhibited stimulation produced by TRH in one experiment. This effect of cyproheptadine was blocked when equimolar concentrations of serotonin was coincubated, whereas serotonin by itself did not affect ACTH secretion. Dopamine (0.1 microM) lowered ACTH accumulation in the medium, which was blocked by the addition of haloperidol. When hydrocortisone was added to the culture, dose-dependent suppression of ACTH secretion was demonstrated. TRH at an equimolar concentration reversed this effect, but, failed to overcome the inhibition induced by a higher concentration of hydrocortisone in cells from one adenoma studied.
    [Show full text]
  • Effects of Corticotropin-Releasing Hormone and Dexamethasone on Proopiomelanocortin Messenger RNA Level in Human Corticotroph Adenoma Cells in Vitro
    Effects of corticotropin-releasing hormone and dexamethasone on proopiomelanocortin messenger RNA level in human corticotroph adenoma cells in vitro. T Suda, … , H Demura, K Shizume J Clin Invest. 1988;82(1):110-114. https://doi.org/10.1172/JCI113557. Research Article The effects of corticotropin-releasing hormone (CRH) and dexamethasone on proopiomelanocortin (POMC) mRNA levels in cultured pituitary adenoma cells were studied in 10 patients with Cushing's disease. As a control, POMC mRNA levels in cells from nonadenomatous tissues were examined in four patients. Human POMC mRNA in the cells was analyzed by Northern blot hybridization. Human POMC DNA probe hybridized with only a single size class of RNA (approximately 1,200 nucleotides) from the adenoma and nonadenoma cells of each patient. The size of POMC mRNA did not change through the culture or after incubation with CRH or dexamethasone. CRH increased POMC mRNA levels in these cells in a dose- and time-dependent manner. The minimum concentration of CRH required to elevate POMC mRNA levels in these cells exposed for 15 h was 0.1 nM. The minimum duration of 1 nM CRH treatment required to increase these levels was 3 h under our conditions. Inhibitory effects of 1 and 10 micrograms/dl dexamethasone on ACTH release and POMC mRNA levels in nonadenoma cells were greater than those in adenoma cells. These results suggest the following: (a) that the mRNA in cultured pituitary adenoma cells is qualitatively the same as that in vivo; (b) that responses of mRNA levels to CRH are time- and dose-dependent;
    [Show full text]
  • Growing up POMC: Pro-Opiomelanocortin in the Developing Brain
    Growing Up POMC: Pro-opiomelanocortin in the Developing Brain Stephanie Louise Padilla Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy under the Executive Committee of the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2011 © 2011 Stephanie Louise Padilla All Rights Reserved ABSTRACT Growing Up POMC: Pro-opiomelanocortin in the Developing Brain Stephanie Louise Padilla Neurons in the arcuate nucleus of the hypothalamus (ARH) play a central role in the regulation of body weight and energy homeostasis. ARH neurons directly sense nutrient and hormonal signals of energy availability from the periphery and relay this information to secondary nuclei targets, where signals of energy status are integrated to regulate behaviors related to food intake and energy expenditure. Transduction of signals related to energy status by Pro-opiomelanocortin (POMC) and neuropeptide-Y/agouti-related protein (NPY/AgRP) neurons in the ARH exert opposing influences on secondary neurons in central circuits regulating energy balance. My thesis research focused on the developmental events regulating the differentiation and specification of cell fates in the ARH. My first project was designed to characterize the ontogeny of Pomc- and Npy-expressing neurons in the developing mediobasal hypothalamus (Chapter 2). These experiments led to the unexpected finding that during mid-gestation, Pomc is broadly expressed in the majority of newly-born ARH neurons, but is subsequently down-regulated during later stages of development as cells acquire a terminal cell identity. Moreover, these studies demonstrated that most immature Pomc-expressing progenitors subsequently differentiate into non-POMC neurons, including a subset of functionally distinct NPY/AgRP neurons.
    [Show full text]