Uptake of [³H]Progesterone and [³H]5α-Dihydroprogesterone by Rat Tissues in Vivo and Analysis of Accumulated Radioactivity: Accumulation of 5α-Dihydroprogesterone by Pituitary and Hypothalamic Tissues

Abstract

These in vivo studies explored the possibility that the metabolism of progesterone to 5alpha-dihydroprogesterone (5alpha-DHP) and 3alpha-hydroxy-5alpha-pregnan-20-one in hypothalamus and pituitary may influence gonadotropin release. [3H]progesterone or [3H]5alpha-DHP was injected iv into ovariectomized or ovariectomized-adrenalectomized rats for 10 0r 30 min. 3H content was determined for plasma, anterior pituitary, medial basal hypothalamus (MBH), cerebral cortex, muscle and uterus. Isotopic dilution analyses of the accumulated 3H were made for progesterone, 5alpha-DHP, 3alpha-hydroxy-5alpha-pregnan-20-one, 20alpha-dihydroprogesterone, 20alpha-hydroxy-5alpha-pregnan-3-one, and 5alpha-pregnane-3alpha, 20alpha-diol on samples from the 10 min groups. With progesterone injections, most of the tissue 3H was distributed among progesterone, 5alpha-DHP, and 3alpha-hydroxy-5alpha-pregnan-20-one. Progesterone was the predominant 3H-steroid in uterus, MBH, cerebral cortex and muscle. [3H]5alpha-DHP was the other major 3H-steroid in MBH and the predominant one in pituitary. In terms of tissue/plasma concentration comparisons, no tissue concentration of [3H]progesterone was greater than that in plasma except for MBH in the ovariectomized-adrenalectomized group. In contrast, [3H]5alpha-DHP levels in pituitary, MBH and cerebral cortex were many fold greater than those in plasma and muscle. MBH and pituitary levels were significantly greater than that in cerebral cortex. With 5alpha-DHP injections, most tissue 3H was associated with 5alpha-DHP and/or 3alpha-hydroxy-5alpha-pregnan-20-one. No [3H]progesterone was detected. [3H]5alpha-DHP predominated in pituitary and MBH, while 3alpha-hydroxy-5alpha-pregnan-20-one predominated in the others. In terms of tissue and plasma concentration comparisons, MBH, pituitary and cerebral cortical concentrations of [3H]5alpha-DHP were markedly higher than plasma, muscle, and uterine levels. Pituitary and MBH concentrations were also greater than that in cerebral cortex. Tissue levels of [3H]3alpha-hydroxy-5alpha-pregnan-20-one were not significantly greater than that in plasma. Thus, 10 min after injection of either [3H]progesterone or [3H]5alpha-DHP, high and significant amounts of 5alpha-DHP are accumulated in pituitary and hypothalamus, but not in uterus, which suggests that its presence may be functionally important in governing progesterone-sensitive processes in these feedback tissues.

Pregnenolone metabolism in rodent embryonic neurons and astrocytes

“…We have not found evidence for the formation of 3p, 501-TH PROG by astrocytes, thus confirming the negative results of Karavolas et al (1976) obtained after incubation of brain tissues with L3H]PROG. However, in the TLC system A used, 3P, 501-TH PROG was hardly separated from PREG, and small yields might have been overlooked.…”

Seizure susceptibility in intact and ovariectomized female rats treated with the convulsant pilocarpine

“…In contrast, under in vivo conditions, brain allopregnanolone levels may not decline so rapidly. In rats, the 5α-reduced metabolites of progesterone, such as allopregnanolone, accumulate in the brain after progesterone administration (Karavolas et al, 1976), consistent with the hypothesis that local intracerebral concentrations of allopregnanolone and its immediate metabolic precursor (5α-dihydroprogesterone) may remain elevated after circulating progesterone levels have declined.…”

Immunohistochemical detection and biological activities of CYP17 (P450c17) in the indifferent gonad of the frog Rana rugosa

“…5␣-and 5␤-DHP are produced from Prog by 5␣-and 5␤-reductase, respectively [48]. 5␣-DHP is one of the major products from Prog in the rat hypothalamus and pituitary [49]. 5␣-DHP binds with high affinity to intracellular Prog receptors and then regulates DNA transcription in the murine brain [50].…”