Biology, Reproductive System Particularities and Hyperadrenocorticism in Domestic Ferret (Mustela Putorius Furo)

Domestic ferrets are common pets all over the globe. They have some particularities in reproductive system and unique endocrinopathy...

reproductive processes in ferrets. It is due to receptors that are found not only in ovaries and testicles, but in cortex part of adrenal gland as well. Adrenal glands are located closely to kidneys and arteria ipsilateralis adrenolumbaris. Right adrenal gland is located very closely to vena cava caudalis. Right adrenal gland is larger than the left one. Sizes of adrenal glands tend to be different between genders of ferrets. In male left adrenal gland is around 7.0 mm, right around 7.5 mm, in female around 5 mm left, around 7 right. Adrenal gland weight tends to increase if ferret is in prolonged oestrus [5,6].

Heat Cycle
Female and male ferrets become sexually active in the first spring after their birth. Usually it is around 9 months of age. Female ferrets are seasonal breeders and come into oestrus under influence of light. Mating activity in ferrets depends on photophase, meaning when length of day exceeds 12 hours, gonadal activity appears. Melatonin provides regulation in hormonal changes. The longer and lighter the day is, the faster ferrets will go into heat.
During this time of year male ferret testis tend to grow bigger, because during cold season they can be retracted in abdominal cavity.
Testosterone level gets higher, as a result body weight increases, specific odour appears and hobs fur tends to get oily. Female ferrets have the same heat cycle pattern -it depends on a day length.
Female ferrets are induced ovulators, meaning they can be brought out of heat by coital stimulus [7,8]. Ovulation appears 30 -36 hours post mating regardless whether fertilization appears or not. If there is no copulation, female ferret will go out of heat when day light decreases. It is dangerous for jill to be in oestrus for long period of time. It can cause oestradiol induced bone marrow suppression.
Levels of oestradiol remain high until the end of the mating season.
Continued high levels of oestradiol can lead to loss of fur, alopecia and bone marrow suppression. In the result anemia may occur [1,4,7]. Anaemia may occur as early as after the first month of heat. An incidence of 50% of jills exhibiting constant oestrus and a rate of 40% mortality has been reported [9]. During breeding season gonadotropin-releasing hormone (GnRH) stimulates the production of the Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), promoting gonads to produce and release either oestradiol (ovaries) or testosterone (testicles). Those hormones exert a negative feedback on hypothalamus and pituitary gland, preventing an excessive secretion of GnRH, LH and FSH. Since ferrets are induced ovulators, during long period of high level of oestradiol, pancytopenia may occur. Jill must be brought out of heat. Prevention isinducing ovulation (with vasectomized hob), ovariohysterectomy, medical management including proligestone injection, busereline acetate injection, insertion of subcutaneous implant containing deslorelin acetate and other less used medications [10].
If proligestone depot injection (50 mg SC) just prior to the breeding season or in jills in oestrus, is considered, repeating of injection must be considered [11]. Return of oestrus is reported in approximately 8% of ferrets 2-5 months after the initial dose.
q24h for 2 days [13]. Slow-releasing devices (implants) containing the gonadotropin-releasing hormone (GnRH) agonist deslorelin acetate are widely used in ferrets, to prevent reproduction in males as well as in females. Available dosages are 4.7 mg and 9.4 mg deslorelin per implant. Implants are placed subcutaneously. The 9.4 mg implants have been used with efficiency for male neutering, with a significant decrease in FSH and testosterone production, size of testicles and a decreased spermatogenesis 1 month later [14]. Ovariohysterectomy is one of the methods used most often.
Gonadectomy surgery techniques in ferrets resemble those for other carnivores.

Physiology of Hyperadrenocorticism
It is proved that hyperadrenocorticism (excessive production of sex steroids) appears in neutered ferrets and it depends on age of neutering as well. After neutering, there is no oetradiol or testosterone to regulate release of GnRH, and secondary LH and FSH. There is no negative feedback, to stop hormonal production.
The chronic elevation in circulating luteinizing hormone is a prerequisite for neoplastic transformation. Hyperadrenocorticism (adrenocortical disease or adrenal disease) is considered as one of the most common diseases in ferrets and is unique to this species. It differs from hyperadrenocorticism in dogs and cats where plasma cortisol concentration is elevated. In ferrets, plasma androstenedione, 17α-hydroxyprogesterone and oestradiol concentrations are increased. The ectopic production of sex steroids by neoplastic adrenocortical tissue causes a syndrome known as adrenal-associated endocrinopathy or hyperadrenocorticism, although more appropriate term for this condition is hyperandrogenism [3]. In the United States and Japan, where most ferrets are gonadectomized at age of 4 -6 weeks, the incidence of adrenocortical neoplasia is 15-22% [17][18][19][20]. In later years, incidence of adrenal disease is up to 70% in the United States. The average age of diagnosis of adrenocortical neoplasia is 3-5 years [16].

Clinical Signs of Hyperadrenocorticism
The most typical and initially seasonal symptoms of hyperadrenocorticism include symmetrical alopecia (getting more permanent over time), vulvar swelling in neutered jills and recurrence of sexual behaviour in neutered males, and there is no sex predilection [16,19,21].

Changes in Adrenal Glands
In approximately 85% of ferrets with hyperadrenocorticism only one adrenal gland is enlarged, without atrophy of the other gland. Histological changes of the adrenal glands vary from nodular hyperplasia to adenoma and adenocarcinoma. Adenomas are well-demarcated lesions composed mainly of polyhedral cells.
Carcinomas are usually large lesions that invade beyond the adrenal capsule and often contain small basophilic ovoid cells, large polyhedral cells, and large cells with vacuolated cytoplasm [22].
Other factors besides prepubertal neutering (gonadectomy) that have been hyphothesized to predispose ferrets to adrenocortical neoplasia include inbreeding at commercial facilities and unnatural photoperiodic stimulation [6]. Adrenocortical neoplasia associated to gonadectomy has been observed in mice, rats, guinea pigs and hamsters as well [25].

Treatment of Hyperadrenocorticism
In treatment of adrenal disease, medical management of adrenal gland tumors has a greater disease-free period compared to adernalectomy [26]. Several medical management options are available including leuprolide acetate injections, desloreline acetate implant, melatonin implant or tablets, anastrazole and finasteride [27]. Usage of desloreline acetate implant is increasing and taking leading part in treatment of adrenal disease. Desloreline acetate mimics GnRH and reduces adrenal stimulation, as a result clinical symptom decrease.