A cellular and molecular basis for the selective desmopressin-induced ACTH release in Cushing’s disease patients: key role of AVPR1b receptor and potential therapeutic implications

Journal of Clinical Endocrinology and Metabolism, 07/25/2013  Review Article

Luque RM et al. – The study aims to determine, for the first time, whether desmopressin acts directly and exclusively on pituitary corticotropinoma cells to stimulate ACTH expression/release, and to elucidate the cellular and molecular mechanisms involved in desmopressin–induced ACTH increase in Cushing’s disease (CD).

The present results provide a cellular and molecular basis to support the desmopressin stimulation test as a reliable, specific test for the diagnosis and post–surgery prognosis of CD.

Furthermore, the data indicates that AVPR1b is responsible of the direct/exclusive desmopressin–stimulatory pituitary effects observed in CD, thus opening the possibility of exploring AVPR1b–antagonists as potential therapeutic tools for CD treatment.

~~~~~~~~

Abstract

  1. RM Luque1,#,
  2. A Ibáñez-Costa1,#,
  3. LM López-Sánchez1,
  4. L Jiménez-Reina2,
  5. E Venegas-Moreno3,
  6. MA Gálvez4,
  7. A Villa-Osaba1,
  8. AM Madrazo-Atutxa3,
  9. MA Japón5,
  10. A de la Riva6,
  11. DA Cano3,
  12. P Benito-López4,
  13. A Soto-Moreno3,
  14. MD Gahete1,
  15. A Leal-Cerro3,*and
  16. JP Castaño1,*

Author Affiliations


  1. 1Department of Cell Biology, Physiology and Immunology University of Córdoba, Reina Sofía University Hospital, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC); CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn); 14014, Córdoba, Spain.

  2. 2Department of Morphological Sciences, University of Córdoba. Córdoba, Spain.

  3. 3Instituto de Biomedicina de Sevilla (IBiS), University Hospital Virgen del Rocío/Consejo Superior de Investigaciones Científicas/University of Seville and Endocrinology, Metabolism and Nutrition Unit, Virgen del Rocío University Hospital, Seville, Spain.

  4. 4Service of Endocrinology and Nutrition, Reina Sofía University Hospital, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC). Córdoba, Spain.

  5. 5Department of Pathology, Virgen del Rocio University Hospital, Seville, Spain.

  6. 6Service of Neurosurgery, Reina Sofía University Hospital Córdoba, Spain.
  1. Address all correspondence and requests for reprints to: Raúl M. Luque and Justo P. Castaño.Department of Cell Biology, Physiology and Immunology; Campus Universitario de Rabanales, Edificio Severo Ochoa (C6), Planta 3; University of Córdoba, E-14014 Córdoba, Spain. Phone:(34)-957218594. Fax: (34)-957218634. E-mails: raul.luque@uco.esjusto@uco.es.
  1. # These authors have codirected this study.

Abstract

Context: Desmopressin is a synthetic agonist of vasopressin-receptors (AVPRs). Desmopressin stimulation test is employed in the diagnosis and post-surgery prognosis of Cushing’s disease (CD). However, the cellular and molecular mechanisms underlying the desmopressin-induced ACTH increase in CD patients are poorly understood.

Objective: 1) To determine, for the first time, whether desmopressin acts directly and exclusively on pituitary corticotropinoma cells to stimulate ACTH expression/release, and 2) to elucidate the cellular and molecular mechanisms involved in desmopressin-induced ACTH increase in CD.

Design: 8 normal-pituitaries (NPs), 23 corticotropinomas, 14 nonfunctioning-pituitary adenomas (NFPA), 17 somatotropinomas and 3 prolactinomas were analyzed for AVPRs-expression by qrtPCR. Primary cultures derived from corticotropinomas, NFPAs, somatotropinomas, prolactinomas and NPs were treated with desmopressin and ACTH-secretion/expression, [Ca2+]i-kinetics, AVPRs-expression and/or proliferative-response were evaluated. The relationship between AVPRs-expression and plasma adrenocorticotropin/cortisol levels obtained from desmopressin-tests was assessed.

Results: Desmopressin affects all functional parameters evaluated in corticotropinoma-cells but not in NPs or other pituitary-adenomas cells. These effects might be due to the dramatic elevation of AVPR1b expression levels found in corticotropinomas. In line with this notion, the use of an AVPR1b-antagonist completely blocked desmopressin-stimulatory effects. Remarkably, only AVPR1b-expression was positively correlated with elevated plasma adrenocorticotropin levels in corticotropinomas.

The present results provide a cellular and molecular basis to support the desmopressin stimulation test as a reliable, specific test for the diagnosis and post-surgery prognosis of CD. Furthermore, our data indicates that AVPR1b is responsible of the direct/exclusive desmopressin-stimulatory pituitary effects observed in CD, thus opening the possibility of exploring AVPR1b-antagonists as potential therapeutic tools for CD treatment.

Footnotes

  • * These authors have codirected this study.

Full Text (PDF)

Johns Hopkins Pituitary Patient Day 2013

Johns Hopkins Pituitary Patient Day

Join us on Saturday, September 28, 2013, for the 5th Annual Patient Education Day at the Johns Hopkins Pituitary Center.

When: Saturday, September 28, 2013
Time: 9:30 a.m.
Location:
Johns Hopkins Mt. Washington Conference Center
5801 Smith Avenue
Baltimore, MD 21209
map and directions

Location of the pituitary gland in the human brain

Location of the pituitary gland in the human brain (Photo credit: Wikipedia)

Patient Education Day Agenda:
9:30 – 10:00 AM REGISTRATION
10:00 – 10:25 AM What is the pituitary gland, where it is located, what it does, and what can go wrong Gary Wand, MD
10:30 – 10:50 AM How pituitary tumors can affect your vision Prem Subramanian, MD, PhD
Vivek Patel, MD, PhD
10:50 – 11:10 AM Cushing disease journey: a patient’s perspective Stacey Hardy
11:15 – 11:40 AM Surgery for Pituitary tumors: from very tiny to very large Alfredo Quinones-Hinojosa, MD
Gary Gallia, MD, PhD
Alessandro Olivi, MD
11:40 – 12:00 PM Radiation therapy: when, why, and how Lawrence Kleinberg, MD
Kristen Redmond, MD
12:05 – 12:25 PM The medications you may be taking (new and old ones): what you need to know Roberto Salvatori, MD
12:30 – 1:25 PM Lunch
1:30 – 3:00 PM PM Round table sessions:
1) Medical therapy (Wand/Salvatori)
2) Surgical therapy (Quinones/Gallia/Olivi)
3) Radiation therapy (Redmond/Kleinberg/Lim)
4) Vision issues (Subramanian/Patel)

*This schedule is subject to change

Please R.S.V.P. by September 13, 2013, vie email (preferred) to PituitaryDay@jhmi.edu  or to Alison Dimick at 410-955-3921.

Reservations will be taken on a first-come, first-serve basis.

Looking at your Doctor’s Notes?

The anterior pituitary is the anterior, glandu...

The anterior pituitary is the anterior, glandular lobe of the pituitary gland. (Photo credit: Wikipedia)

Acronyms or abbreviations for “Pituitary”

PIT: pituitary
P: Pituitary
PI: pituitary
PT: pituitary
PG: pituitary gland
PIT: pituitary gland
PS: pituitary stalk
NP: normal pituitary
PT: pituitary tumors
PV: pituitary venous
SP: sellar pituitary
PA: pituitary-adrenal
PA: pituitary adenoma
PEX: Pituitary Extract
ap: anterior pituitary
PA: pituitary adenomas
PA: pituitary apoplexy
PAs: pituitary adenomas
PP: posterior pituitary
oPRL: ovine pituitary PRL
phTSH: pituitary human TSH
Pitx1: pituitary homeobox 1
Ptx1: pituitary homeobox 1
BPG: brain-pituitary-gonad
HP: hypothalamo-pituitary
H-P: hypothalamic-pituitary
HP: hypothalamic-pituitary
HP: hypothalamus/pituitary
PAA: pituitary-adrenal axis
A.P.L.: anterior pituitary like
AP: anterior pituitary lobe
pgh: pituitary growth hormone
AP: anterior pituitary gland
APG: anterior pituitary gland
BPE: bovine pituitary extract
EPE: equine pituitary extract
PA: pituitary-adrenocortical
PP: posterior pituitary lobe
AP: Anterior pituitary glands

Pregnancy and pituitary disorders

Pituitary and pineal glands

Pituitary and pineal glands (Photo credit: Wikipedia)

Z Karaca, F Tanriverdi, K Unluhizarci and F Kelestimur
+ Author Affiliations

Department of Endocrinology,
Erciyes University Medical School, 38039 Kayseri, Turkey
(Correspondence should be addressed to F Kelestimur; Email: fktimur@erciyes.edu.tr)

Abstract

Major hormonal changes emerge during pregnancy. The pituitary gland is one of the most affected organs with altered anatomy and physiology. The pituitary gland is enlarged as a result of lactotroph hyperplasia. Due to physiological changes in the pituitary and target hormone levels, binding globulins, and placental hormones, hormonal evaluation becomes more complex in pregnant women. As a consequence of physiological hormonal changes, the evaluation of pituitary functions in pregnant women is quite different from that done in the prepregnant state. Pituitary adenomas may cause problems by their hormone secretion that affects the mother and the fetus besides causing an increased risk of tumor growth.

Furthermore, diagnosis, course, and treatment of pituitary diseases point out differences. The changes in anatomy and physiology of the pituitary gland during pregnancy are reviewed.

Pituitary disorders namely Cushing’s disease; acromegaly; prolactinoma; TSH-secreting, gonadotropin-producing, and clinically nonfunctioning adenomas; craniopharyngioma; and Sheehan’s syndrome, which is one of the most common causes of hypopituitarism, lymphocytic hypophysitis, and hypopituitarism, in relation to pregnancy are discussed. Being aware of all this information will prevent any serious problems which mother and child will be exposed to.

Read the entire article here: http://www.eje-online.org/content/162/3/453.full

From Bangladesh ~ Pituitary Adenoma: When headache is a headache

Location of the pituitary gland in the human brain

Location of the pituitary gland in the human brain (Photo credit: Wikipedia)

“Got headache? Take a paracetamol and get relieved in a short while.”

This is common practice in our country. Almost everyone has had a headache, but rarely headache becomes a headache in our lives. Not all headaches require doctor’s attention but sometimes it represent the tip of a huge iceberg.

Mr Shafiul Islam, 38 years of age, an active male developed a gradual onset of headache, which worsened at the morning, followed by vomiting. He visited a general practitioner and took prescribed medicines, but that failed to cure the symptoms. Rather he was gradually experiencing loss of outer side vision of both eyes.

When he revisited a doctor and was advised for MRI of brain he was diagnosed with a core of “Pituitary Macrodenoma,” a tumor of a hormone producing gland of brain. Then Shafiul was referred to Neurosurgeon of Comfort Nursing home Assistant Professor Dr Moshiur Rahman, who decided to perform operation for removal of the tumor after the initial evaluation.

The pituitary gland is an endocrine gland about the size of a pea and weighing 5 grams (0.18 oz) in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity (sella turcica). The pituitary gland secretes nine hormones. A pituitary adenoma is a slow growing and less harmful tumor arising from cells in the pituitary gland. Because they originate from cells in the pituitary gland, which is the master hormone gland, they often cause problems related to hormonal dysfunction.

Some pituitary tumors result in excessive production and over-secretion of hormones, which can result in a variety of syndromes. A large proportion of these tumors, however, do not produce any functional hormones, but instead grow to a size where they cause symptoms because they compress surrounding structures. For these reasons, larger pituitary tumors (called macroadenomas) often present with headache, visual loss and pituitary gland dysfunction.

The specific cause of pituitary adenoma development is unknown, although they are likely to be caused in part by random mutations in cells of the pituitary gland. Surgery is the first line of treatment for many symptomatic pituitary tumors in patients that are good surgical candidates, especially in patients with nonfunctioning macroadenomas.

Dr Moshiur approached the tumor by entering through nasal opening with the help of ENT specialist Associate Professor Dr Sajol Ashfaq, under general aenesthesia (fully unconscious) done by Aenesthesiologist Associate Professor Dr Shamsul Alam. After elevation of a thin membrane over the nasal partition and breaking a bone in the base of the skull they got a vision of the tumor through endoscope. After that, the tumor was removed through the nose. After three days of post-operative care, the patient was discharged. All his symptoms, headache, vomiting and poor vision improved dramatically and he got back to his normal life.

Dr Moshiur Rahman said: “The surgical approach for removing pituitary tumours is usually an endonasal (through the nostril) transsphenoidal (through the sphenoid sinus) approach. This procedure is Endoscopic Transnasal Transphenoidal Pituitary Adenomectomy, which is a safe, minimally invasive but effective, modern treatment option for Pituitary Adenoma, with few side effects and short post-operative hospital stay. This latest technology is being practiced in some centres of the capital for last few years.”

He also said, he performed three operations before successfully with no long term adverse effect. He also paid gratefulness to Associate Professor Dr Sajol Ashfaq and Associate Professor Dr Shamsul Alam for their sincere and great effort.

Once, people had to go outside of the country for this operation. Nowadays, this operation is often performed by many neurosurgeons of the capital. A few centres have also developed to provide these facilities of operation. People can take this oppurtunity confidently by choosing a competent surgical team.