The blood supply and direction of flow in the hypophyseal portal system has been studied over many years on laboratory animals and human cadaver specimens with injection and vascular corrosion casting methods.

[2][3][4] Other evidence indicates that capillary perivascular spaces of the median eminence and arcuate nucleus are contiguous, potentially facilitating hormonal messages between systemic blood and the ventral hypothalamus.

Hormone-exchanging blood vessels between the hypothalamus and the pituitary gland, similar to those of the hypophyseal portal system, can be observed in early developmental stages of the fetus.

In a specimen at week 11.5, the median eminence and infundibular stem contained the compound, suggesting the existence of the fully developed portal system.

[4] The following is a list of hormones that rely on the hypophyseal portal system to indirectly mediate their function by acting as a means of transportation from various nuclei of the hypothalamus to the anterior pituitary.

[7] Over- or under-function as well as insufficiencies of the hypothalamus or the pituitary gland can cause a negative effect on the ability of the hypophyseal portal system to exchange hormones between both structures rapidly.

Occlusions and other issues in the blood vessels of the hypophysial portal system can also cause complications in the exchange of hormones between the hypothalamus and the pituitary gland.

[10] It has been suggested, nonetheless, that damage to the pituitary stalk leads to an obstruction of blood flow in the hypophyseal portal system and contributes to this defective state.

[11] In Erdheim–Chester disease, cells of the immune system called histiocytes proliferate at an abnormal rate causing a plethora of symptoms and, in more severe cases, death.