Message Number: SG17586 | New FHL Archives Search

From: Sukie Crandall
Date: 2006-06-13 18:26:20 UTC
Subject: [ferrethealth] PDE 11A and adrenal tumors
To: FHL <ferrethealth@smartgroups.com>

Trying this from email, 6/13/06, 2:26 EST US.
(It will still differ from email use by general membership but may
give us moderators some feeling for the functions today.)

I am sending this today because I have heard back from two ferret
veterinary researchers (one studying ferret genetics, and one who is
known for studying ferret adrenals, past and present). Both think
that this enzyme indicates an interesting thing to study in ferrets
even though this original study was in humans.

I have written to the contact person and hope that it becomes
possible to get a reply. Later i hope to search down study authors to
ask if needed, but have been very short on time so can not promise. I
have passed this on to some of the world's ferret adrenal disease
study authors, but do not have addresses for some others due just to
not knowing them at all, so if others want to show them the release,
please, feel free to do so.

If the ferret vulnerability for hormonal adrenal neoplasia is there
originally because of PDE11A being deficient or damaged (and then the
documented route of neutering and over-exposure to light, less
melatonin, more LH and FSH, then adrenal over-stimulation and
irritation takes place then PERHAPS there may be an approach based on
either breeding those who are not deficient in the enzyme, or on
somehow replacing or supplementing the enzyme, which may be an
optimal prophylactic approach. Certainly, if this deficit applies to
ferrets we might get a new route for approaches.

Take it with a boulder of salt since we don't know yet if it applies
to ferrets or not.

Press Release (public) from Eurekalert!:

> Public release date: 11-Jun-2006
> [ Print Article | E-mail Article | Close Window ]
>
> Contact: Robert Bock or Marianne Glass Miller
> bockr@...
> 301-496-5133
> NIH/National Institute of Child Health and Human Development
> Lack of key enzyme associated with development of rare tumor
>
>
>
> Researchers at the National Institutes of Health have discovered
> that a rare tumor of the adrenal glands appears to result from a
> genetic deficiency of an important enzyme. The enzyme is one of a
> class of enzymes involved in halting a cell's response to hormones
> and appears to stop cells from dividing.
> The study, published in Nature Genetics, was conducted by
> researchers in NIH's National Institute of Child Health and Human
> Development. The NIH group collaborated with scientists from the
> Mayo Clinic, the Cochin Institute in Paris, the University of
> Paris, Ohio State University in Columbus, and the Universitaire
> Vaudois in Lausanne, Switzerland, in collecting samples from
> patients with rare adrenal disorders. Scientists from Sapio
> Sciences in York, Pennsylvania, assisted in the analysis of the data.
> In conducting the study, the researchers used gene arrays to
> analyze the DNA of patients with a rare tumor of the adrenal
> glands, known as micronodular adrenocortical hyperplasia, explained
> the study's senior author, Constantine Stratakis, M.D., D(Med)Sc,
> Chief of NICHD's Section on Endocrinology and Genetics. The
> researchers also used the technology to analyze samples of the
> patients' tumors.
> The researchers found four patients who had mutant copies of a gene
> that contains the information for Phosphodiesterase 11A (PDE11A).
> Phosphodiesterases are a family of enzymes involved in "switching
> off" a cell's response to hormones, Dr. Stratakis explained.
> For a hormone to affect the cell, it must first bind to a molecule,
> or receptor, on the cell's surface, analogous to how a key fits
> into a lock. This action triggers the cell to produce substances
> known as cyclic nucleotides. These function as "second messengers,"
> often stimulating the cell to begin an activity. In the case of
> adrenal cells, cyclic nucleotides, such as cyclic AMP and cyclic
> GMP, may stimulate cell growth or other activities. Once the
> activity has ended, phosphodiesterases degrade the cyclic
> nucleotides, thereby halting the cell's response to the hormone.
> In the study, the patients' tumors were made up of cells that were
> deficient in the enzyme PDE11A. This enzyme halts cyclic nucleotide
> production in adrenal cells as well as in other kinds of cells in
> the body. Because they lacked PDE11A, the patients' adrenal cells
> had higher levels of cyclic nucleotides. The researchers believe
> that these higher cyclic nucleotide levels led to the formation of
> tumors.
> The gene for PDE11A contains the information needed to make 4
> slightly different forms of the enzyme. The form of the enzyme that
> was mutated in the patients who took part in the study was found in
> large amounts in normal adrenal glands and in even larger amounts
> in normal prostate glands, Dr. Stratakis added. Other forms of
> PDE11A are found in several other tissues, including the testes,
> skeletal muscle, and the heart.
> Dr. Stratakis noted that although the evidence associating the
> mutation in the gene for PDE11A to the development of adrenal
> tumors was very strong, the study was not capable of proving that
> the mutation actually caused the tumors.
> In their article, the researchers wrote that drugs used to treat
> erectile dysfunction interfere with the functioning of PDE11A. The
> researchers noted that PDE11A "is partially inhibited" by the drug
> tadalafil and "weakly" inhibited by sildenafil. They added that
> there are no reports in the medical literature of malfunctioning
> adrenal glands or increased adrenal cell growth in users of these
> drugs.
> "However, detailed clinical studies addressing this potential
> complication are currently lacking," they wrote.
> Dr. Stratakis and his colleagues are currently planning studies to
> determine if differences in the gene for PDE11A might influence an
> individual's cancer risk.
>
> ###
> The NICHD sponsors research on development, before and after birth;
> maternal, child, and family health; reproductive biology and
> population issues; and medical rehabilitation. For more
> information, visit the Institute's Web site at http://
> www.nichd.nih.gov/.
>
> The National Institutes of Health (NIH) -- The Nation's Medical
> Research Agency -- includes 27 Institutes and Centers and is a
> component of the U. S. Department of Health and Human Services. It
> is the primary federal agency for conducting and supporting basic,
> clinical, and translational medical research, and it investigates
> the causes, treatments, and cures for both common and rare
> diseases. For more information about NIH and its programs, visit
> http://www.nih.gov.


-- Sukie (not a vet, and not speaking for any of the below in my
private posts)
Recommended health resources to help ferrets and the people who love
them:
Ferret Health List
http://www.smartgroups.com/groups/ferrethealth
FHL Archives
http://ferrethealth.org/archive/
AFIP Ferret Pathology
http://www.afip.org/ferrets/index.html
Miamiferrets
http://www.miamiferret.org/fhc/
International Ferret Congress Critical References
http://www.ferretcongress.org




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