Health Research Center
Physiology, Endocrinology, Clinical Chemistry
Hypoxia is common with preterm birth and may lead to long-term effects on the adult hypothalamic-pituitary-adrenal (HPA) axis that are sexually dimorphic due to neonatal androgens. Although the adult rat adrenal does not express appreciable CYP17 activity, the neonatal rat adrenal may synthesize androgens that could be a critical local factor in the development of adrenal function. We evaluated these phenomena by pretreating the neonatal rats on postnatal days (PD) 1, 6, 13, 20 with flutamide (a non-steroidal androgen receptor antagonist) at a standard or a high-dose (10 mg/kg or 50 mg/kg) compared to vehicle control. One day later, neonatal rats were exposed to acute hypoxia and blood was sampled. Our studies suggest that neonatal androgens play a role in regulation of adrenal function that is sexually dimorphic and changes during early development.
Premature birth is a major public health problem worldwide and can lead to transient adrenal insufficiency. The stress of premature birth includes the inability to control blood glucose and maintain normal oxygenation leading to hypoxia. Corticosteroid administration enhances surfactant production and improves oxygenation in preterm humans. However, corticosteroids can also have negative consequences. We have validated a rat model of separation and hypoxia on post-natal day (PD) 2 that emulates the stress and treatment of hypoxia in the preterm human infant. We hypothesized that the role of endogenous glucocorticoids in our neonatal rat model of preterm birth can be evaluated using the novel selective glucocorticoid receptor (GR) antagonist CORT113176 (Corcept) which is devoid of progesterone receptor effects. The differential effects of CORT113176 based on age and target tissue indicate that GR regulation changes in early development in our animal model of human prematurity. These findings may have significant implications in the treatment of hypoxia and transient adrenal insufficiency in the preterm infant as well as give insight into the nuances of the control of glucocorticoid receptor function.
Late-night salivary cortisol (LNSC) measured by enzyme immunoassay (EIA) is established as a reliable screening test and recommended as a first-line test for Cushing’s syndrome. However, liquid chromatography-tandem mass spectrometry (LCMS), validated to measure salivary cortisol (F) and cortisone (E), has been proposed to be superior diagnostically as well as helpful in detecting saliva contaminated with topical hydrocortisone (i.e. cortisol). So far we have measured EIA-F, LCMS-F, and LCMS-E in 913 consecutive late-night saliva samples from patients suspected of Cushing’s syndrome. EIA-F appears to be superior to LCMS-F in identifying CD patients with milder hypercortisolism using established diagnostic cutoffs. Neither LCMS-E nor F/E ratio improved the diagnostic sensitivity in newly diagnosed CD or persistent/recurrent CD after pituitary surgery. We suggest that late-night salivary cortisol measured by EIA provides the best sensitivity for CD diagnosis.
Ashley Gehrand, MS
Jonathan Phillips, BS
M3 Medical Student
Pathway Research Project
M2 Medical Student
Pathway Research Project
M1 Medical Student
Josh Kannakeril, MD
Clinical Endocrine Fellow
Clinical Fellows (Research)
- Thomas P. Segerson, MD – Research Fellow
- Victor O. Waters, MD – Critical Care Fellow
- Santo J. Diaz, MD – Critical Care Fellow
- Manoj H. Majmudar, MD – Critical Care Fellow
- Robert C. Brickner, MD – Endocrine Metabolic Fellow
- Pennapa Chan, MD – Endocrine-Metabolic Fellow
- Scott Brock, MD – Endocrine-Metabolic Fellow
- Sandra L. Ettema, MD, PhD, CCC-SLP – Otolaryngology Resident
- Vidya Kidambi, MD – Endocrine-Metabolic Fellow
- Ty Carroll, MD – Endocrine-Metabolic Fellow
- Jay Mepani, MD-Endocrine-Metabolic Fellow
- Michael Einstein, MD – GI Fellow
- Giovanna Caprirolo, MD – Pediatric Critical Care Fellow
- Mohamed Tahsin Jouhari, MD – Pediatric Critical Care Fellow
- Neil Reisinger, MD – Chief Medical Resident
- Nebiyu Biru, MD – Chief Medical Resident
- Satyanisth Agrawal, MD – GI Fellow
- Brian Rajca, MD – GI Fellow
- Julia Leo, MD – GI Fellow
- Veena Kumaravel, MD – GI Fellow
- Jonathan Fahler, MD – GI Fellow
Post Doctoral Research Fellow
Paula. E. Papanek, PhD
Eric D. Bruder, MS – University of Wisconsin, Milwaukee
Medical Student Research Trainees – Medical College of Wisconsin
- Timothy P. Roarty
- Maryam Ivanoff
- Steven C. Griffen
- Saeid Kohandarvish
- Mark H. Rossing
- Sandra K. Doepker
- Pedro Lucero
- Anne Nagler
- Jody VanHoof
- Karl Johnson (Clinician Scientist Pathway Advisor, 2011-2014; T35 Training Grant from National Heart, Lung, Blood Institute (NHLBI))
- Jonathan Bodager (Clinical Scientist Pathway Advisor, 2013-2016)
- Nasha Nensey (Physician Scientist – Molecular and Cellular Research Pathway Advisor, 2014-2017)
- Adam Goldenberg (Physician Scientist – Molecular and Cellular Research Pathway); Advisor, 2016-2019; T35 Training Grant from the National Heart, Lung, Blood Institute (NHLBI)
- Christine Huyhn (Quality Improvement and Patient Safety Pathway); Research Advisor 2017, Dr. Michael J. Dunn Medical Student Summer Research Training Fellowship)
Undergraduate Summer Trainees
- A. Joseph Tector, III – Indiana University
- Edward Stauber (1997 Endocrine Society Student Research Fellow) – University of Wisconsin
- Genevieve Schmitt – College of the Holy Cross
- Seth Auger – University of Dayton
- Judson Werner – University of Wisconsin
- Michael Patrick Kehoe – University of Wisconsin
- Jonathan Klinger – Marquette University
- John P. Tucker – University of Wisconsin
- Jennifer Taylor – Northwestern University
- Michael Nord – University of Minnesota
- Kimberli Kamer – University of Wisconsin
- Mitchell Guenther – Lawrence University
- Christopher Wean – Renssalaer Polytechnic Institute
- Kathan Chintamaneni – Washington University of St. Louis
- Kristin Prewitt – University of Wisconsin
- Thomas Gessert – University of Wisconsin
- Mack Jablonski – Lawrence University
- Cole Leonovicz – University of Miami
- Emily Waples – Duke University
- Minhal Gardezi – Wellesley College
- Maya Guenther – Lawrence University
- Matthew Schulgit – University of Wisconsin
- Hana Siddiqui – University of Wisconsin
Periodic hypoxia, intermittent pain, and caffeine in male and female neonatal rats: corticosterone, insulin resistance, and hepatic gene expression.
(Gehrand AL, Phillips JM, Raff H.) Am J Physiol Regul Integr Comp Physiol. 2023 Jun 01;324(6):R708-R719 PMID: 36912474 03/14/2023
Genetic background in the rat affects endocrine and metabolic outcomes of Bisphenol F exposure.
(Wagner VA, Holl KL, Clark KC, Reho JJ, Dwinell MR, Lehmler HJ, Raff H, Grobe JL, Kwitek AE.) Toxicol Sci. 2023 May 16 PMID: 37191987 05/16/2023
Salivary Cortisol Dynamics After Mild Traumatic Brain Injury.
(Musacchio S, Kallenbach MD, Huber DL, Raff H, Johnson BD, Leddy J, McCrea MA, Meier TB, Nelson LD.) J Head Trauma Rehabil. 2023 Jan 21 PMID: 36696236 01/26/2023
Sleep restriction during opioid abstinence affects the hypothalamic-pituitary-adrenal (HPA) axis in male and female rats.
(Raff H, Glaeser BL, Szabo A, Olsen CM, Everson CA.) Stress. 2023 Jan;26(1):2185864 PMID: 36856367 SCOPUS ID: 2-s2.0-85150079770 03/02/2023
Characterization of the Dahl salt-sensitive rat as a rodent model of inherited, widespread, persistent pain.
(Ferrari LF, Rey C, Ramirez A, Dziuba A, Zickella J, Zickella M, Raff H, Taylor NE.) Sci Rep. 2022 Nov 11;12(1):19348 PMID: 36369350 PMCID: PMC9652451 SCOPUS ID: 2-s2.0-85141733424 11/13/2022
Late Night Salivary Cortisol in the diagnosis of neoplastic hypercortisolism (including cyclic Cushing's syndrome).
(Raff H.) Pituitary. 2022 Oct;25(5):698-700 PMID: 35334030 SCOPUS ID: 2-s2.0-85127277574 03/26/2022
Lipid signatures of chronic pain in female adolescents with and without obesity.
(Gonzalez PA, Simcox J, Raff H, Wade G, Von Bank H, Weisman S, Hainsworth K.) Lipids Health Dis. 2022 Aug 30;21(1):80 PMID: 36042489 PMCID: PMC9426222 SCOPUS ID: 2-s2.0-85136987097 08/31/2022
(Medda R, Raff H, Shaker J, Guda N.) Am J Gastroenterol. 2022 May 01;117(5):813-814 PMID: 35080511 SCOPUS ID: 2-s2.0-85129996587 01/27/2022
Opioids and pituitary function: expert opinion.
(Gadelha MR, Karavitaki N, Fudin J, Bettinger JJ, Raff H, Ben-Shlomo A.) Pituitary. 2022 Feb;25(1):52-63 PMID: 35066756 SCOPUS ID: 2-s2.0-85123498706 01/24/2022
Interaction of chronic pain, obesity and time of day on cortisol in female human adolescents.
(Raff H, Phillips J, Simpson P, Weisman SJ, Hainsworth KR.) Stress. 2022 Jan;25(1):331-336 PMID: 36330600 SCOPUS ID: 2-s2.0-85141327101 11/05/2022
Glucocorticoid Receptor Antagonist Alters Corticosterone and Receptor-sensitive mRNAs in the Hypoxic Neonatal Rat.
(Gehrand AL, Phillips J, Welhouse KD, Siddiqui H, Schulgit M, Hoffman J, Hunt H, Raff H.) Endocrinology. 2022 Jan 01;163(1) PMID: 34791109 SCOPUS ID: 2-s2.0-85122710601 11/19/2021
Consensus on diagnosis and management of Cushing's disease: a guideline update.
(Fleseriu M, Auchus R, Bancos I, Ben-Shlomo A, Bertherat J, Biermasz NR, Boguszewski CL, Bronstein MD, Buchfelder M, Carmichael JD, Casanueva FF, Castinetti F, Chanson P, Findling J, Gadelha M, Geer EB, Giustina A, Grossman A, Gurnell M, Ho K, Ioachimescu AG, Kaiser UB, Karavitaki N, Katznelson L, Kelly DF, Lacroix A, McCormack A, Melmed S, Molitch M, Mortini P, Newell-Price J, Nieman L, Pereira AM, Petersenn S, Pivonello R, Raff H, Reincke M, Salvatori R, Scaroni C, Shimon I, Stratakis CA, Swearingen B, Tabarin A, Takahashi Y, Theodoropoulou M, Tsagarakis S, Valassi E, Varlamov EV, Vila G, Wass J, Webb SM, Zatelli MC, Biller BMK.) Lancet Diabetes Endocrinol. 2021 Dec;9(12):847-875 PMID: 34687601 PMCID: PMC8743006 SCOPUS ID: 2-s2.0-85122111053 10/24/2021