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PubMed1986

Pulsatile release of luteinizing hormone and testosterone in male ferrets.

The temporal organization of LH and testosterone secretion was examined in male European ferrets. Hormone levels were measured in frequent blood samples taken via an indwelling jugular cannula from sexually mature and castrated ferrets. Intact ferrets discharge LH and testosterone in discrete pulses, but the frequency and amplitude of these pulses vary within and between individual males. The average frequency of LH pulses was 1.14 +/- 0.25 pulses/h, with an amplitude of 1.59 +/- 0.23 ng/ml in 11 ferrets. Testosterone pulse frequency and amplitude were 0.62 +/- 0.04 pulses/h and 16.96 +/- 2.5 ng/ml, respectively. The frequency, amplitude, and duration of hormone pulses were similar during the light and dark phases of the light-dark cycle. LH and testosterone peaks were temporally coupled with LH pulses preceding testosterone pulses by 10-20 min. However, not all LH pulses evoked a rise in testosterone. Frequently, trains of 2 or more LH pulses gave rise to a single testosterone pulse. Castration provoked a rapid increase in the frequency of LH pulses, and the interpulse interval became strikingly uniform within hours after orchidectomy. The amplitude of LH pulses, in contrast, increased gradually over the first 6 postcastration days and then plateaued at about 4.5 ng/ml. These findings demonstrate that LH pulses constitute functionally important signals to the testis, as evidenced by temporally related increments in testosterone secretion. Moreover, distinct differences in the development of the postcastration rise in the frequency and amplitude of LH pulses suggest that testosterone operates via multiple mechanisms to regulate LH release in the adult male. Finally, this study emphasizes the utility of the ferret as an animal model to study neural determinants of LH release in the male.

Animals↗
PubMed1988

Sexual maturation in the female ferret: circumventing the gonadostat.

The purpose of this study was to examine the role of circulating 17 beta-estradiol in the regulation of pituitary gonadotropin secretion and, hence, ovarian maturation in immature female ferrets. The hypersensitive negative feedback relationship between the ovaries and the hypothalamo-pituitary axis in developing ferrets was disrupted by infusion of a specific antiserum to 17 beta-estradiol. The effect of this treatment on gonadotropin secretion and ovarian morphology was contrasted with that observed in intact age-matched control females treated with a nonimmune gamma-globulin preparation. Infusion of the antibody into intact immature ferrets caused, within 48 h, an increase in pulsatile secretion of LH to 0.67 +/- 0.06 pulses/h over that observed in intact females treated with control gamma-globulin (0.13 +/- 0.06 pulses/h). This increase in pulse frequency was similar to that observed 48 h after ovariectomy of young animals (0.70 +/- 0.12 pulses/h). Furthermore, this level of gonadotropin secretion in antibody-treated animals resulted in stimulation of antral follicle growth in ovaries of these females. Ferrets treated with specific antiserum to 17 beta-estradiol showed a significant increase in numbers of ovarian follicles greater than 0.3 mm in diameter compared to those in ovaries of females treated with control gamma-globulin. These data strongly suggest that the limiting event at puberty in the ferret is the rise in gonadotropin secretion which is allowed by the pubertal decrease in efficacy of 17 beta-estradiol to inhibit gonadotropin secretion.

Animals↗
PubMed1989

Prolactin or dopamine mediates the induction of puberty by long days in female ferrets.

The role of PRL in sexual maturation of female ferrets was examined in these studies. Longitudinal profiles of PRL secretion were obtained by thrice weekly blood sampling of intact female ferrets undergoing photoperiod-stimulated development as well as age-matched control females which remained in nonstimulatory short days. Two additional groups of intact females, one in each photocycle, were treated with the dopamine agonist drug bromocriptine throughout the study. The relationship between developmental changes in PRL secretion and the critical pubertal decrease in the efficacy of estradiol (E2) inhibitory feedback on LH secretion was studied by using additional groups of females which were ovariectomized and treated with E2 implants (OVX + E2). These latter females were housed in either long or short day photoperiods; some were treated with bromocriptine, the remainder were treated with the vehicle only. Results of this study revealed that PRL secretion in ferrets does not change acutely with an abrupt increase in day length. After 4 weeks of exposure to long days, however, a marked increase in PRL secretion occurred. This increased secretion of PRL was contemporaneous with the onset of pubertal ovarian activity in intact females and with the escape of LH from the negative feedback of E2 in OVX + E2-treated females. The further observation that pharmacological blockade of the long day-induced rise in PRL secretion also prevented the pubertal onset of ovarian activity suggested that PRL may play a critical role in the induction of puberty in this species. The mechanism by which bromocriptine prevented puberty induction was illustrated in the OVX + E2-treated ferrets in stimulatory photoperiod. The drug treatment prevented the pubertal decrease in the efficacy of E2 negative feedback on LH. These studies suggest an important interaction between the dopamine-PRL system and the GnRH-LH system in the regulation of sexual maturation of female ferrets.

Animals↗
PubMed1992

Sex difference in the effect of mating on c-fos expression in luteinizing hormone-releasing hormone neurons of the ferret forebrain.

The pulsatile secretion of LH was previously found to rise in female ferrets after receipt of an intromission, whereas in males that achieved an intromission, both LH and testosterone secretion were either reduced or unchanged. We sought to determine whether this sexually dimorphic pattern of LH secretion reflects a sex difference in the effect of mating on the activity of forebrain neurons that secrete LHRH. Immunocytochemical methods were used to localize the nuclear protein product of the immediate early gene, c-fos, as an index of increased neuronal activity after mating. Nuclear FOS immunoreactivity (FOS-IR) was monitored in LHRH-IR neurons as well as other non-LHRH forebrain neurons. In confirmation of previous reports, LHRH-IR perikarya in ferrets of both sexes were located medially along the base of the brain at rostral, medial, and caudal levels of the preoptic-hypothalamic continuum. In each of these regions a significantly higher percentage of LHRH-IR neurons was colabeled with nuclear FOS-IR in mated than in unpaired females. By contrast, an equivalent low percentage of LHRH-IR neurons was colabeled with FOS-IR in mated and unpaired male ferrets. Significantly more FOS-IR neurons (not colabeled with LHRH) were detected in the bed nucleus of the stria terminalis, the medial preoptic area, the dorsal-medial hypothalamus, and the medial amygdala (MA) of mated vs. unpaired females. By contrast, mating significantly augmented FOS-IR only in the MA of male ferrets. The results suggest that the sexually dimorphic pattern of LH secretion that occurs in ferrets after mating reflects a selective activation of LHRH neurons in the female forebrain. This sex-specific increase in the responsiveness of LHRH neurons to mating may depend on input from a limbic circuit which includes the medial amygdala, bed nucleus of the stria terminalis, and medial preoptic area.

Animals↗
PubMed1997

Sexually dimorphic processing of somatosensory and chemosensory inputs to forebrain luteinizing hormone-releasing hormone neurons in mated ferrets.

The ferret is a reflexively ovulating species in which mating induces a preovulatory LH surge in the estrous female but significantly decreases LH secretion in the breeding male. This sexually dimorphic hormonal response is reflected in a sex difference in Fos-like immunoreactivity (Fos-IR) in forebrain LHRH and non-LHRH neurons after mating. We used dual immunocytochemistry for Fos and LHRH to determine whether the sex dimorphism occurs in the initial detection and transmission or in the central processing of sensory stimuli associated with mating? We also assessed the ability of chemosensory cues alone to augment neuronal Fos-IR in the ferret forebrain. Breeding male and female ferrets were paired, whereupon the male partner achieved an intromission lasting for 16-90 min. Mated male and female subjects were always perfused 90 min after the onset of the male's intromission. Additional male and female subjects were placed alone in a cage in which an opposite sex ferret in breeding condition had been housed for 48 h. Other control ferrets were placed alone in a clean cage. Chemosensory-stimulated and unpaired control subjects were perfused 90 min after being placed in their respective cages. In both sexes mating augmented neuronal Fos-IR in the granular layer of the main olfactory bulb, the caudal thalamic central tegmental field, and the medial amygdala, regions situated early in the putative input pathway to mediobasal hypothalamic LHRH neurons. Neuronal Fos-IR was also increased in these same forebrain regions (the central tegmental field excluded) in both sexes after exposure to chemosensory cues alone. However, more central components of this input pathway, including the preoptic area, the bed nucleus of the stria terminalis, and the ventrolateral portion of the ventromedial hypothalamus as well as the mediobasal hypothalamic LHRH neurons themselves were activated by mating only in the female. In estrous females, exposure only to chemosensory stimuli from a breeding male augmented Fos-IR in the preoptic area and the ventrolateral portion of the ventromedial hypothalamus, but not in the bed nucleus of the stria terminalis or mediobasal hypothalamic LHRH neurons. In breeding males, exposure only to chemosensory cues from an estrous female failed to affect Fos-IR in any of these proximal components of the input pathway or in LHRH neurons themselves. These results suggest that the sex dimorphism in mating-induced LH secretion reflects a sex difference in the central processing of genital-somatosensory stimuli and possibly of chemosensory inputs as well.

Animals↗
PubMed2002

Hepatobiliary inflammation, neoplasia, and argyrophilic bacteria in a ferret colony.

Hepatobiliary disease was diagnosed in eight of 34 genetically unrelated cohabitating pet ferrets (Mustela putorios furo) during a 7-year period. The eight ferrets ranged in age from 5 to 8 years and exhibited chronic cholangiohepatitis coupled with cellular proliferation ranging from hyperplasia to frank neoplasia. Spiral-shaped argyrophilic bacteria were demonstrated in livers of three ferrets, including two with carcinoma. Sequence analysis of a 400-base pair polymerase chain reaction product amplified from DNA derived from fecal bacteria from one ferret demonstrated 98% and 97% similarity to Helicobacter cholecystus and Helicobacter sp. strain 266-1 , respectively. The clustering of severe hepatic disease in these cohabitating ferroes suggests a possible infectious etiology. The role of Helicobacter species and other bacteria in hepatitis and/or neoplasia in ferrets requires further study.

Animals↗
PubMed2004

Transcription factor GATA-4 is a marker of anaplasia in adrenocortical neoplasms of the domestic ferret (Mustela putorius furo).

Adrenocortical neoplasms are a common cause of morbidity in neutered ferrets. Recently we showed that gonadectomized DBA/2J mice develop adrenocortical tumors that express transcription factor GATA-4. Therefore, we screened archival specimens of adrenocortical neoplasms from neutered ferrets to determine whether GATA-4 could be used as a tumor marker in this species. Nuclear immunoreactivity for GATA-4 was evident in 19/22 (86%) of ferret adrenocortical carcinomas and was prominent in areas exhibiting myxoid differentiation. Normal adrenocortical cells lacked GATA-4 expression. Two other markers of adrenocortical tumors in gonadectomized mice, inhibin-alpha and luteinizing hormone receptor, were coexpressed with GATA-4 in some of the ferret tumors. No GATA-4 expression was observed in three cases of nodular hyperplasia, but patches of anaplastic cells expressing GATA-4 were evident in 7/14 (50%) of tumors classified as adenomas. We conclude that GATA-4 can function as a marker of anaplasia in ferret adrenocortical tumors.

Adrenal Cortex Neoplasms↗
PubMed1989

Evidence that oestrogen exerts an equivalent negative feedback action on LH secretion in male and female ferrets.

Gonadally intact male ferrets in breeding condition, which received an aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD) s.c. in Silastic capsules, had significantly more LH pulses and higher mean LH concentrations in plasma than did control males implanted with empty capsules. Aromatase activity in the hypothalamus + preoptic area and temporal lobe was strongly suppressed by ATD treatment whereas circulating concentrations of testosterone and oestradiol were not affected. These results suggest that oestradiol, formed via neural aromatization of circulating testosterone, contributes to the feedback regulation of LH secretion in breeding male ferrets just as oestradiol of ovarian origin controls LH secretion in females. No sex difference was observed in the rate at which mean plasma LH concentrations rose after the removal from gonadectomized ferrets of s.c. Silastic capsules containing oestradiol. Daily s.c. injections of oestradiol in oil caused an equivalent, dose-dependent inhibition of LH pulse frequency and mean LH concentrations in plasma of male and female ferrets. These findings suggest that the negative feedback control of pulsatile LH secretion by oestrogen is not sexually differentiated in this reflexly ovulating species. The ferret appears to differ from spontaneously ovulating mammalian species in which the female is generally more sensitive than the male to the inhibitory feedback action of oestradiol on LH secretion.

Androstatrienes↗
PubMed1999

Nonsurgical collection and nonsurgical transfer of preimplantation embryos in the domestic rabbit (Oryctolagus cuniculus) and domestic ferret (Mustela putorius furo).

The objective of this study was to develop nonsurgical methods of embryo collection and transfer in domestic rabbits (Oryctolagus cuniculus) and domestic ferrets (Mustela putorius furo) to serve as models for use in mammals in which surgical procedures are the usual means for applying embryo transfer technology. Specially designed transcervical catheters were used together with a fibre optic endoscope to visualize and then catheterize the rabbit and ferret cervices. Five consecutive transcervical uterine flushes in each of eight superovulated female rabbits 78-89 h after an ovulatory injection of LH resulted in the retrieval of 187 embryos, for an average of 23 embryos per rabbit. A total of 116 embryos were nonsurgically transferred to the uteri of ten recipients, and resulted in 23 young (20%). Eight rabbits (80%) produced young with an average litter size of 2.88 (range 1-7). Ten consecutive transcervical uterine flushes in each of 37 female ferrets 145-178 h after an ovulatory injection of hCG resulted in the retrieval of 324 embryos, an average of 8.76 embryos per ferret. A total of 251 embryos from 27 donors were nonsurgically transferred to the uteri of 31 recipients, and resulted in 65 young (26%). Twenty-eight of the recipients (90%) were initially pregnant, as indicated by postpartum necropsies, and twenty-two ferrets (71%) produced young. The average litter size was 2.95 (range 1-7). This is the first report of live births resulting from the nonsurgical collection of embryos from a donor followed by nonsurgical transfer of those same embryos to a synchronous recipient. The methods reported here can serve as models for use in other mammals in which direct visualization and manipulation of the cervix are not possible, and will be particularly useful in endangered species.

Animals↗
PubMed2000

Effect of gonadal steroids on pituitary LH secretion and mediobasal hypothalamic GnRH mRNA in ferrets.

In vitro release and content of GnRH in mediobasal hypothalamic slices are reduced by ovariectomy of female ferrets but are not affected by castration of male ferrets in breeding condition. The aim of the present study was to determine whether this sex difference reflects a sexually dimorphic effect of gonadal steroids on mediobasal hypothalamic GnRH mRNA content of male and female ferrets killed 4 weeks after gonadectomy, either with or without steroid hormone replacement. This time interval exceeds the 6-10 days needed for increments in plasma LH concentrations to stabilize after gonadectomy of ferrets of both sexes. In situ hybridization using an (35)S-labelled oligoprobe complementary to the human GnRH coding region showed that the number of mediobasal hypothalamic neurones and the cellular content of GnRH mRNA did not differ significantly among groups of male and female ferrets that were either in breeding condition or that had been gonadectomized and treated with sex steroids or oil vehicle. These results indicate that gonadal hormones regulate mediobasal hypothalamic GnRH biosynthesis and release in both sexes via post-transcriptional events that may include GnRH mRNA translation or the conversion of pre-pro GnRH precursor into mature GnRH.

Analysis of Variance↗
PubMed1988

Differential effects of testosterone, 5 alpha-dihydrotestosterone and oestradiol-17 beta on plasma concentrations of LH in castrated ferrets.

The biological activity of testosterone often depends on the conversion of testosterone within the target cell to an androgenic or oestrogenic metabolite. The purpose of this study was to compare the relative ability of testosterone and two of its metabolites, dihydrotestosterone (DHT) and oestradiol, to suppress LH secretion in castrated male ferrets. Castrated ferrets were treated with five different doses of steroid by implanting various numbers of s.c. silicone elastomer capsules packed with either testosterone, DHT or oestradiol. The lowest dose of oestradiol (0.1 mm capsule length/100 g body weight, mean estimated total release rate of 25 ng/day) significantly suppressed plasma concentrations of LH in castrated ferrets. Higher amounts of DHT (2.5 mm capsule length/100 g body weight, mean estimated total release rate of 88 ng/day) were required for a significant reduction in plasma concentrations of LH. Concentrations of LH were also significantly lowered by testosterone when administered at a 2.5 mm capsule length/100 g body weight; however, estimated total release rate was 312 ng/day from these capsules. The fact that oestradiol was more effective than DHT, and that DHT was more effective than testosterone in inhibiting LH secretion in castrated ferrets, suggests that in gonadally intact ferrets, testosterone may be converted to DHT or oestradiol within target cells that mediate steroid negative feedback on LH secretion.

Animals↗
PubMed1990

Emesis-related biochemical and histopathological changes induced by cisplatin in the ferret.

Cisplatin is an effective antineoplastic agent that causes severe vomiting due to unknown mechanism. The ferret, an animal model useful in the determination of emetic activity, was used to clarify the emesis-related biochemical and histopathological changes that were induced by cisplatin. Cisplatin (5 to 10 mg/kg) was administered intraperitoneally and a 7-10 mg/kg i.p. dose evoked dose-dependent emesis in the ferret. Almost all cisplatin-vomiting episodes occurred within a 6 hour observation period. All ferrets receiving cisplatin in this study died within 3-5 days. Significant increases in ileal mucosal levels of serotonin and norepinephrine were observed in cisplatin-treated ferrets. There were no significant changes in the levels of serotonin and dopamine in the gastric mucosa. Also, karyorrhexis was observed in the epithelial cells of the ileum and in the lymph follicles of the spleen of cisplatin-treated ferrets. These significant biochemical and pathological changes in the ileum may play an important role in cisplatin-induced emesis.

Animals↗
PubMed1997

Vomiting induction by ipecac syrup in dogs and ferrets.

The dog has been used as an experimental animal in emesis research. In this study, we analyzed the emetic effects of ipecac syrup using a smaller animal, the ferret, and compared its response to that of the dog. Dogs and ferrets were divided into 4 groups (n = 4, each). Each group was given either 0.1, 0.25, 0.5, or 1.0 ml/kg of ipecac syrup, and the latency and numbers of retching and vomiting were recorded. Animals given an equal volume of saline served as controls. The numbers of vomiting and retching increased dose-dependently in both dogs and ferrets, and there was no difference in latency and numbers of vomiting between them. The numbers of retching were greater in ferrets than in dogs at > or = 0.25 ml/kg. Taking these results into consideration, the ferret seems to be as useful as the dog in studies on emetic effects of ipecac syrup.

Animals↗
PubMed1992

MR lymphography with iron oxide compound AMI-227: studies in ferrets with filariasis.

OBJECTIVE: The purpose of this study was to assess the MR lymphographic potential of AMI-227 to reduce the signal intensity of hyperplastic inflammatory lymph nodes by using ferrets with filariasis as the animal model. Both interstitial and IV modes of administration were studied. MATERIALS AND METHODS: Twelve ferrets were infected with the filaria Brugia malayi and six control ferrets were injected with super-paramagnetic iron oxide AMI-227, either interstitially or IV. Signal intensities of the left popliteal lymph node, left hamstring muscle, and left inguinal fat were measured before, 48 hr after, and up to 138 days after contrast injection with the use of both spin-echo and gradient-echo techniques. The signal intensity data were statistically analyzed. The lymph nodes, liver, spleen, and lungs were studied with light and electron microscopy. RESULTS: Forty-eight hours after the interstitial injection of AMI-227, the signal intensities of the ipsilateral popliteal nodes of the infected and control ferrets were significantly reduced (p less than .0005) without significant changes in the signal intensities of the surrounding tissues on both spin-echo and gradient-echo MR images. No nodal signal reduction occurred with the IV route of injection in ferrets. Light microscopy revealed iron to be localized within nodal marginal zones exclusively. Lymphatic trunks were visualized after interstitial injection. Signal reduction persisted to our end point at 138 days. CONCLUSION: AMI-227 shows regional specificity with significant enhancement of nodal structures and demonstrates potential as an interstitial MR lymphographic agent.

Animals↗
PubMed2004

Effect of sevoflurane on hemodynamic and cardiac energetic parameters in ferrets.

OBJECTIVE: To determine the effect of sevoflurane on cardiac energetic and hemodynamic parameters in ferrets. ANIMALS: 7 healthy domesticated ferrets. PROCEDURE: Sevoflurane was used as the sole anesthetic agent for general anesthesia in ferrets. Standard midline laparotomy and median sternotomy were performed to permit instrumentation. Myocardial blood flow was determined by use of colored microsphere technology. Measurements and blood samples were obtained at 1.25%, 2.5%, and 3.75% expired concentration of sevoflurane. RESULTS: A dose-dependent decrease in arterial blood pressure, left ventricular pressure, systemic vascular resistance, aortic flow, and dp/dt (an index of contractility) was detected as expired concentration of sevoflurane increased. Heart rate, central venous pressure, coronary vascular resistance, myocardial oxygen extraction ratio, and tau (the time constant of relaxation) were unchanged. Cardiac external work decreased, as did myocardial oxygen consumption, causing increased cardiac efficiency at higher concentrations of sevoflurane. CONCLUSIONS AND CLINICAL RELEVANCE: Sevoflurane caused minimal and predictable cardiovascular effects in ferrets without increasing myocardial metabolic demands. Data obtained from this study have not been previously reported for a species that is being commonly used in cardiovascular research. These findings also support use of sevoflurane as a safe inhalant anesthetic in ferrets for clinical and research settings.

Animals↗
PubMed2000

Acute ibuprofen toxicosis in a ferret.

A 20-month-old 1.44-kg (3.2-lb) castrated male ferret was examined because of vomiting, defecating in an abnormal location, dyspnea, and signs of depression. Within 5 minutes of initial evaluation, the ferret became nonresponsive to all stimuli except deep pain. Despite intensive supportive treatment, the ferret died. Toxicologic analyses for ibuprofen were performed on serum, urine, and liver, using gas chromatography and mass spectrophotometry. Serum ibuprofen concentrations were 245 micrograms/g before and 269 micrograms/g after death. Acute ibuprofen toxicosis may cause severe lethargy progressing to coma, apnea, and death in ferrets. Ibuprofen toxicosis should be considered in differential diagnoses for ferrets with signs of depression, with or without clinical signs of gastrointestinal tract dysfunction.

Analgesics, Non-Narcotic↗
PubMed1987

Bacterial adherence to the upper respiratory tract of ferrets infected with influenza A virus.

A ferret model was used to study bacterial adherence in animals with influenza. Ferrets were inoculated intranasally with influenza A3/Hong Kong/1/68 virus. Antiviral serum antibodies were apparent by Day 5. On Days 3, 5, 7, 9, and 11, three virus-inoculated and two uninoculated controls were anesthetized, exsanguinated, and decapitated, and the lower jaw was removed. Each animal was inoculated intranasally with a 1-ml suspension containing 20 mg (dry wt) of either 3H-labeled Staphylococcus aureus or 3H-labeled group B Streptococcus type Ia and incubated for 45 min at ambient temperature. In animals challenged with staphylococci, 80% of the original inoculum remained free in suspension; of the remaining 20%, the distribution in the upper respiratory tracts of virus-infected and control animals was significantly different. Of the staphylococci remaining in the nasopharynx of control animals, 74% was present in mucinous plugs, 11% was bound to host cells present in washes of the nasal cavity, and 15% was released by protease treatment of the nasopharynx. Of the staphylococci remaining in the upper respiratory tract of virus-infected ferrets, 36% was recovered in plugs, 24% was bound to cells in nasal washes, and 40% was released by enzyme treatment. Overall, adherence-positive staphylococci represented 64% of recoverable bacteria in virus-infected ferrets versus 26% in controls. Adherence was increased twofold (Days 5 and 7) to threefold (Days 3, 9, and 11) in virus-infected ferrets compared to uninfected controls. In contrast, only 7% of the original streptococcal inoculum was recovered from virus-infected and uninfected control animals and virus infection did not enhance streptococcal adherence except for an approximately threefold increase that was seen on Day 11.

Animals↗
PubMed1987

Peripheral lymphedema in ferrets infected with Brugia malayi.

This study examines the production and persistence of peripheral lymphedema in ferrets experimentally infected with Brugia malayi. In 14 of 18 ferrets inoculated 2 or more times with infective larvae, lymphedema developed in the inoculated paw or paw and lower leg. In 5 of these ferrets lymphedema had persisted for 8 to 18 months at the time of necropsy. Lymphedema rarely was observed following a single inoculation of larvae or in microfilaremic ferrets. The results suggest that the ferret may be a useful experimental animal for the study of chronic lymphostatic disorders in filariasis.

Animals↗