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In the mature female ferret hormonally induced changes leading the the onset of estrus begin when the light/dark signals (there is more day than night) occurring during early springtime are transmitted from the eyes to the hypothalamic area of the brain. The hypothalamus releases a hormone that stimulates the pituitary gland. The pituitary, in turn, secretes two hormones into the bloodstream - follicle stimulating hormone (FSH) and luteininzing hormone (LH). When the first of these hormones, FSH, reaches the ovary, it causes the eggs or ova, which are produced in follicles within the ovaries, to ripen in preparation for release into the uterus. FSH, along with small amount of LH, stimulates the ovaries to produce and release the sex hormone estrogen.

Estrogen brings about the changes in both the internal and external reproductive organs. It promotes enlargement of the uterus and increases the thickness of the mucosal lining. There is considerable proliferation of uterine blood vessels and consequently a marked increase in the blood supply to that areas. In addition, tiny glands that secrete mucus develop.

Externally, estrogen stimulation brings about a swelling of the vulva, which continues until it is about 50 times its unstimulated size.

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