From:
"Sukie Crandall"
Date: 2007-06-01 06:42:00 UTC
Subject: [ferrethealth] Re: Ingesting estrogen from prey?
To: ferrethealth@yahoogroups.com
BTW, in the next IFC Symposium which happens later this month, Dr. Bob Wagner will be
discussing adrenal disease and the endocrinology involved, including work with meds like
Lupron Depot, Suprelorin Depot, and some related ones.
Here are the abstracts of three such studies:
BEGIN QUOTES
Am J Vet Res. 2005 May;66(5):910-4.
Clinical and endocrine responses to treatment with deslorelin acetate implants in ferrets
with adrenocortical disease.
Wagner RA,
Piche CA,
Jochle W,
Oliver JW.
Division of Laboratory Animal Resources, 3500 Terrace St, S1049 BST, University of
Pittsburgh, Pittsburgh, PA 15261, USA.
OBJECTIVE: To evaluate the clinical and endocrine responses of ferrets with adrenocortical
disease (ACD) to treatment with a slow-release implant of deslorelin acetate. ANIMALS: 15
ferrets with ACD. PROCEDURE: Ferrets were treated SC with a single slow-release, 3-mg
implant of deslorelin acetate. Plasma estradiol, androstenedione, and 17-
hydroxyprogesterone concentrations were measured before and after treatment and at
relapse of clinical signs; at that time, the adrenal glands were grossly or
ultrasonographically measured and affected glands that were surgically removed were
examined histologically. RESULTS: Compared with findings before deslorelin treatment,
vulvar swelling, pruritus, sexual behaviors, and aggression were significantly decreased or
eliminated within 14 days of implantation; hair regrowth was evident 4 to 6 weeks after
treatment. Within 1 month of treatment, plasma hormone concentrations significantly
decreased and remained decreased until clinical relapse. Mean time to recurrence of
clinical signs was 13.7 +/- 3.5 months (range, 8.5 to 20.5 months). In 5 ferrets, large
palpable tumors developed within 2 months of clinical relapse; 3 of these ferrets were
euthanatized because of adrenal gland tumor metastasis to the liver or tumor necrosis.
CONCLUSIONS AND CLINICAL RELEVANCE: In ferrets with ACD, a slow-release deslorelin
implant appears promising as a treatment to temporarily eliminate clinical signs and
decrease plasma steroid hormone concentrations. Deslorelin may not decrease adrenal
tumor growth in some treated ferrets. Deslorelin implants may be useful in the long-term
management of hormone-induced sequelae in ferrets with ACD and in treatment of
animals that are considered at surgical or anesthetic risk.
PMID: 15934621 [PubMed - indexed for MEDLINE]
J Am Vet Med Assoc. 2001 Apr 15;218(8):1272-4.
Leuprolide acetate treatment of adrenocortical disease in ferrets.
Wagner RA,
Bailey EM,
Schneider JF,
Oliver JW.
Department of Laboratory Animal Resources, School of Health Sciences, University of
Pittsburgh, PA 15261, USA.
OBJECTIVE: To determine the effects of leuprolide acetate, a long-acting gonadotropin-
releasing hormone analog, in ferrets with adrenocortical diseases. DESIGN: Case series.
ANIMALS: 20 ferrets with adrenocortical disease diagnosed on the basis of clinical signs
and plasma sex hormone concentrations. PROCEDURE: Ferrets were treated with leuprolide
(100 microg, IM, once), and plasma hormone concentrations were measured before and 3
to 6 weeks after treatment. RESULTS: Leuprolide treatment resulted in significant
reductions in plasma estradiol, 17 alpha-hydroxyprogesterone, androstenedione, and
dehydroepiandrosterone concentrations and eliminated or reduced clinical signs
associated with adrenocortical disease. Decreases in vulvar swelling, pruritus, and
undesirable sexual behaviors and aggression were evident 14 days after treatment; hair
regrowth was evident by 4 weeks after treatment. The response to treatment was
transitory, and clinical signs recurred in all ferrets. Mean +/- SEM time to recurrence was
3.7 +/- 0.4 months (range, 1.5 to 8 months). CONCLUSIONS AND CLINICAL RELEVANCE:
Results suggest that leuprolide can be safely used to temporarily eliminate clinical signs
and reduce sex hormone concentrations in ferrets with adrenocortical diseases. However,
the safety of long-term leuprolide use in ferrets has not been investigated, and the long-
term effects of leuprolide in ferrets with nodular adrenal gland hyperplasia or adrenal
gland tumors are unknown.
PMID: 11330611 [PubMed - indexed for MEDLINE]
J Am Vet Med Assoc. 1994 Sep 1;205(5):703-7. Links
Comment in:
J Am Vet Med Assoc. 1994 Dec 15;205(12):1660-1.
Evaluation of serum estradiol concentrations in alopecic ferrets with adrenal gland tumors.
Wagner RA,
Dorn DP.
Division of Laboratory Animal Resources, University of Pittsburgh, PA 15261.
Seventeen ferrets were examined because of progressive bilaterally symmetric alopecia
that was nonpruritic. Dermatologic and endocrinologic testing were used to determine the
cause of the alopecia. Resting cortisol, testosterone, and thyroxin concentrations and
results of ACTH stimulation tests were found to be within reference range limits
established for this species. High serum estradiol concentrations were found to be a
reliable indicator of adrenal cortical neoplasia in these ferrets.
PMID: 7989239 [PubMed - indexed for MEDLINE]
END QUOTES
Here are some recent studies and a re-capping of earlier work with many more available to
you on the web in PubMed and elsewhere (See links section of the FHL for several ways to
find such studies.):
BEGIN QUOTES
J Am Anim Hosp Assoc. 2007 Mar-Apr;43(2):78-84.
Ultrasonographic visualization of the adrenal glands of healthy ferrets and ferrets with
hyperadrenocorticism.
Kuijten AM,
Schoemaker NJ,
Voorhout G.
Division of Avian and Exotic Animal Medicine, Department of Clinical Science of
Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The
Netherlands.
A protocol was developed to compare the ultrasonographic characteristics of the adrenal
glands of 21 healthy ferrets and 37 ferrets with hyperadrenocorticism. By using specific
landmarks, the adrenal glands were imaged in 97% of the cases. The adrenal glands of
ferrets with hyperadrenocorticism had a significantly increased thickness, with changes in
shape, structure, and echogenicity compared to the adrenal glands of healthy ferrets.
Based on the findings of the study, adrenal glands may be classified as abnormal when
they have a rounded appearance, increased size of the cranial/caudal pole (thickness >3.9
mm), a heterogeneous structure, increased echogenicity, and/or signs of mineralization.
PMID: 17339284 [PubMed - in process]
J Am Vet Med Assoc. 2006 Dec 1;229(11):1743-8.
Effects of melatonin administration on the clinical course of adrenocortical disease in
domestic ferrets.
Ramer JC,
Benson KG,
Morrisey JK,
O'Brien RT,
Paul-Murphy J.
Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin,
Madison, WI 53706, USA.
OBJECTIVE: To evaluate the effect of oral administration of melatonin on clinical signs,
tumor size, and serum steroid hormone concentrations in ferrets with adrenocortical
disease. DESIGN: Noncontrolled clinical trial. ANIMALS: 10 adult ferrets with clinical signs
of adrenocortical disease (confirmed via serum steroid hormone concentration
assessments). PROCEDURES: Melatonin (0.5 mg) was administered orally to ferrets once
daily for 1 year. At 4-month intervals, a complete physical examination; abdominal
ultrasonographic examination (including adrenal gland measurement); CBC; serum
biochemical analyses; and assessment of serum estradiol, androstenedione, and 17alpha-
hydroxyprogesterone concentrations were performed. Serum prolactin and
dehydroepiandrosterone sulfate concentrations were evaluated at the first, second, and
last examinations, and serum cortisol concentration was evaluated at the first and last
examinations. RESULTS: Daily oral administration of melatonin greatly affected clinical
signs of adrenocortical disease in ferrets; changes included hair regrowth, decreased
pruritus, increased activity level and appetite, and decreased vulva or prostate size. Mean
width of the abnormally large adrenal glands was significantly increased after the 12-
month treatment period. Recurrence of clinical signs was detected in 6 ferrets at the 8-
month evaluation. Compared with pretreatment values, serum 17alpha-
hydroxyprogesterone and prolactin concentrations were significantly increased and
decreased after 12 months, respectively. CONCLUSIONS AND CLINICAL RELEVANCE:
Results suggest that melatonin is a useful, easily administered, palliative treatment to
decrease clinical signs associated with adrenocortical disease in ferrets, and positive
effects of daily treatment were evident for at least an 8-month period. Oral administration
of melatonin did not decrease adrenal gland tumor growth in treated ferrets.
PMID: 17144819 [PubMed - indexed for MEDLINE]
Vet Pathol. 2006 Mar;43(2):97-117. Links
Gonadectomy-induced adrenocortical neoplasia in the domestic ferret (Mustela putorius
furo) and laboratory mouse.
Bielinska M,
Kiiveri S,
Parviainen H,
Mannisto S,
Heikinheimo M,
Wilson DB.
Department of Pediatrics, Box 8208, Washington University School of Medicine, 660 South
Euclid Avenue, St. Louis, MO 63110, USA.
Sex steroid-producing adrenocortical adenomas and carcinomas occur frequently in
neutered ferrets, but the molecular events underlying tumor development are not well
understood. Prepubertal gonadectomy elicits similar tumors in certain inbred or
genetically engineered strains of mice, and these mouse models shed light on
tumorigenesis in ferrets. In mice and ferrets, the neoplastic adrenocortical cells, which
functionally resemble gonadal steroidogenic cells, arise from progenitors in the
subcapsular or juxtamedullary region. Tumorigenesis in mice is influenced by the inherent
susceptibility of adrenal tissue to gonadectomy-induced hormonal changes. The chronic
elevation in circulating luteinizing hormone that follows ovariectomy or orchiectomy is a
prerequisite for neoplastic transformation. Gonadectomy alters the plasma or local
concentrations of steroid hormones and other factors that affect adrenocortical tumor
development, including inhibins, activins, and Mullerian inhibiting substance. GATA-4
immunoreactivity is a hallmark of neoplastic transformation, and this transcription factor
might serve to integrate intracellular signals evoked by different hormones. Synergistic
interactions among GATA-4, steroidogenic factor-1, and other transcription factors
enhance expression of inhibin-alpha and genes critical for ectopic sex steroid production,
such as cytochrome P450 17alpha-hydroxylase/17,20 lyase and aromatase. Cases of
human adrenocortical neoplasia have been linked to precocious expression of hormone
receptors and to mutations that alter the activity of G-proteins or downstream effectors.
Whether such genetic changes contribute to tissue susceptibility to neoplasia in neutered
ferrets and mice awaits further study.
PMID: 16537928 [PubMed - indexed for MEDLINE]
with the full text here:
http://www.vetpathology.org/cgi/content/full/43/2/97
END QUOTES
Basically, anything that increases the production of LH sets the stage for adrenal tumor
growth, but there is evidence that some ferrets also have at least one type of genetic
variant that can increase endocrinological tumors in other species, so also may in ferrets.
The output of LH (and also of FSH, which among other things seems to be able to cause
bone mass loss) can be increased by being altered. Also, the production of LH and FSH
naturally increases when the amount of melatonin in the body decreases. Melatonin is
another hormone. Melatonin is produced in response the darkness, so you can see where
changing seasons would normally induce estrus and rut. When there are gonads they can
yell back at the pituitary when it is time to decrease the LH and FSH levels again with their
own hormonal responses. Without something to decrease those high levels irritation
occurs and so on...
There is huge body of work on the functions of melatonin in the body, and more are being
found.
One other thing that might also interest you is work into domestication itself. It looks like
one of the primary changes of domestication is that the adrenal gland less readily puts out
the steroids associated with jumpiness. There are also common physical features found
such are white splotches (neural crest genetic variants), neotany (child-like appearance),
etc. An out-dated term which is still used as a label in relation to that is "star gene" when
there are actually multiple variants (but there is a similar term with very different meaning
so watch out for that).
http://jhered.oxfordjournals.org/cgi/content/abstract/72/4/267
http://8e.devbio.com/article.php?id=223
http://www.floridalupine.org/publications/PDF/trut-fox-study.pdf
http://www.americanscientist.org/template/AssetDetail/assetid/15642/page/
6;jsessionid=aaa5LVF0
http://www.freerepublic.com/focus/news/807641/posts
etc.
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