The metabolic clearance rate, head and brain extractions, and brain distribution and metabolism of progesterone in the anesthetized, female monkey (Macaca mulatta).

The brain distribution and metabolism of progesterone were studied in female, rhesus monkeys. Adult monkeys were anesthetized with ketamine and were given a constant infusion of [3H]- or [14C] progesterone. Blood samples were obtained from cannulae inserted into the carotid artery, the jugular vein and lateral (transverse) sinus. The metabolic clearance rate of progesterone was 295 +/- 49 (S.E.) 1/day. The head extraction of progesterone was 30.4 +/- 8.3% (S.E.) and the brain extraction 26.0 +/- 9.18% (S.E.). The peripheral conversion ratios of progesterone to 20alpha-hydroxypregn-4-en-3-one (20alpha-OHP) and 5alpha-pregnan-3,20-dione (5alpha-DHP) were 10.0 +/- 1.3% (S.E.) and 2.4 +/- 0.3% (S.E.), respectively. These same conversion ratios for across the head were 4.8 +/- 1.0% (S.E.) and 1.5 +/- 0.6% (S.E.) and for across the brain 5.0 +/- 0.7% (S.E.) and 2.2 +/- 0.6% (S.E.). The concentration of radioactive progesterone was 2-5 times higher in brain tissues compared to the carotid arterial blood. The tissue concentrations of radioactive progesterone compared to a cerebrum 'control' sample: was lower in the central gray (P less than 0.05); were the same for the amygdala, hippocampus, preoptic-anterior hypothalamus, cerebellum, hypothalamus, thalamus, and anterior pituitary; and were higher in the cervical spinal cord, optic chiasm, mesencephalon, medulla oblongata and pons (P less than 0.1). The distribution pattern of 20alpha-OHP formed from progesterone was similar to that of progesterone. 5alpha-DHP formed from progesterone had a different distribution than progesterone, being highest in the central gray area. High concentrations of 5alpha-DHP were also observed in the mesencephalon, medulla oblongata and hypothalamus and low values in the anterior pituitary. Infusions of [3H]20alpha-OHP and [3H]5alpha-DHP were used to evaluate the in vivo metabolism of progesterone by different brain areas. [3H]Estradiol infused into one monkey had its highest concentration in the anterior pituitary which was 20 times higher than in the carotid arterial blood.