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

Billiar, Reinhart B.; Little, Brian; Kline, Irene T.; Reier, Paul J.; Takaoka, Yoshiro; White, Robert J.

doi:10.1016/0006-8993(75)90880-x

Cited by 40 publications

(15 citation statements)

References 44 publications

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“…A similar obsvervation was re corded by Tabei and Heinrichs [29] who studied progeste rone metabolism by 700 g cell-free homogenates of the hy pothalamus of male rhesus monkeys. At saturating concen trations of progesterone the 'conversions' (ng-formed) of progesterone to 20a-OHP or 5a-DHP are approximately the same (table V, VI), similar to that observed by us in in vivo studies of the rhesus monkey [2]. If one assumes that the major subcellular site of 'conversion' is in the fraction with the highest ratio of product to precursor, the most ac tive fraction of the conversion of progesterone to 5a-DHP is the wash of the nuclei (i. e. 'supernatant of the nuclei'; ta ble VI).…”

Section: Discussionsupporting

confidence: 69%

“…The isolation by thin-layer chromatography (TLC) and quantitation of radioactive progeste rone, 20a-hydroxy-pregn-4-ene-3-one (20a-OHP), 5a-pregnane-3,20-dione (5a-DHP) and estradiol from the acetone and benzene extracts were as reported [2]. For isolation of [3H]androstenedione, [3H]testosterone and [JH]estrone in the [JH]-androstenedione stud ies, the extracts of the subcellular fractions were first chromato graphed in the TLC system of chlorofrom-methanol, 98:2.…”

Section: Methodsmentioning

confidence: 99%

“…The homogenates and supernatant fractions were extracted with benzene as previously described [2]. The isolation by thin-layer chromatography (TLC) and quantitation of radioactive progeste rone, 20a-hydroxy-pregn-4-ene-3-one (20a-OHP), 5a-pregnane-3,20-dione (5a-DHP) and estradiol from the acetone and benzene extracts were as reported [2].…”

Section: Methodsmentioning

confidence: 99%

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In situ Subcellular Distribution and Metabolism of Progesterone, Estradiol and Androstenedione in the Vascularly Separated and Isolated Hypothalamus of the Female Rhesus Monkey

Billiar

Takaoka²,

Johnson

et al. 1981

Neuroendocrinology

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A neurosurgical procedure has been developed for the vascular isolation of the hypothalamus-thalamus region of the rhesus monkey brain. The circulation to the left and right halves of the hypothalamus was also isolated and each half of the hypothalamus was perfused simultaneously, but separately, with a dextran-blood solution which contained radioactive gonadal steroids. The hypothalamus in situ efficiently converted [³H]androstenedione to [³H]estrone and this aromatization was inhibited by the presence of androsta-1,4,6-triene-3,17-dione (ATD) in the perfusate. [³H]Progesterone was metabolized predominately to 5α-pregnane-3,20-dione (5α-DHP) and 20α-hydroxypregn-4-ene-3-one (20α-OHP). Subceilular fractionation of the hypothalamus after the in situ perfusion with [³H]-progestin or [³H]estradiol to the hypothalamus of estrogen-treated ovariectomized monkeys or oil-treated ovariectomized monkeys, respectively, indicated that the retention of [³H]estradiol in the nucleus was a saturable, limited-capacity phenomenon. No saturable subceilular distribution of [³H]progesterone or [³H]R 5020 was observed. This latter observation might be attributable to the presence of a progesterone receptor in too small a concentration to be detected by the methods used.

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Section: Discussionsupporting

confidence: 69%

Section: Methodsmentioning

confidence: 99%

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In situ Subcellular Distribution and Metabolism of Progesterone, Estradiol and Androstenedione in the Vascularly Separated and Isolated Hypothalamus of the Female Rhesus Monkey

Billiar

Takaoka²,

Johnson

et al. 1981

Neuroendocrinology

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“…For instance, it is well known that PROG originating in the periphery is taken up by the nervous system in considerable amounts (Billiar et al, 1975). We observed that females have higher levels of PROG in the PNS and CNS than males, which reflect their plasma concentration.…”

Section: Modulation Of the Synthesis And Metabolism Of Progesterone Imentioning

confidence: 71%

Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions

Melcangi

Giatti

Calabrese

et al. 2014

Progress in Neurobiology

114

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Progesterone is synthesized and actively metabolized in the central and peripheral nervous system, into neuroactive steroid metabolites, such as dihydroprogesterone, allopregnanolone and isopregnanolone. Progesterone and/or its metabolites exert a variety of effects acting as physiological regulators of neuronal and glial development and plasticity, controlling reproduction, neuroendocrine events, mood and affection. In addition, these neuroactive steroids maintain neural homeostasis and exert neuroprotective actions. In agreement, metabolic pathways of progesterone are affected by modifications in the level of gonadal hormones and by pathology or injury with a regional specificity and in a sex-dimorphic way. Therefore, observations here summarized may provide a background to design sex-specific therapies based on progesterone metabolites. On this point of view, considering that one of the major limits of a therapy based on neuroactive steroids could be modifications in their plasma levels and their consequent peripheral effects, pharmacological treatments aimed to increase their levels in the nervous system could provide an interesting therapeutic option.

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“…Autoradiography (JH)Estradiol and (JH)R5020 were purchased from New En gland Nuclear Corporation and were purified by thin-layer chro matography [2,13]. Radioinert estradiol and progesterone were pu rified by crystallization and their melting points determined in a Hoover capillary melting point apparatus. '…”

Section: Hypothalamic Perfusion With (Jh)estradiol or (Jh)r5020formentioning

confidence: 99%

In situ Estradiol and Progestin (R5020) Localization in the Vascularly Separated and Isolated Hypothalamus of the Rhesus Monkey

Garris

Billiar

Takaoka³

et al. 1981

Neuroendocrinology

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A neurosurgical procedure has been developed for vascular isolation of the hypothalamus-thalamus region of the rhesus monkey brain. Utilizing this preparation, the left and right halves of the hypothalamus were perfused simultaneously, but separately, with a dextran-blood solution. Radiolabeled steroids were directly perfused in the dextran-blood into either the left or right half of the hypothalamus. Studies with radiolabeled gonadal steroids indicate that the majority of the carotid circulation is confined to the hypothalamus-thalamus area in this brain preparation and the cross-circulation of labelled steroids between the left and right sides of the hypothalamus is less than 10%. The usefulness of the preparation is illustrated by an autoradiographic study of the in situ hypothalamic distribution of (³H)estradiol in ovariectomized rhesus monkeys and of the synthetic progestin (³H)R5020 in estrogen-primed, ovariectomized rhesus monkeys. The direct perfusion of the (³H) steroids into the hypothalamus greatly increases the sensitivity of such a study compared to systemic administration of the (³H) steroids. The perfusion of one-half of the hypothalamus with (³H) steroid and the other half with (³H)steroid plus radioinert steroids permits in 1 animal, acting as its own control, the examination of a saturable distribution of a gonadal steroid in the rhesus monkey hypothalamus.

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

Cited by 40 publications

References 44 publications

In situ Subcellular Distribution and Metabolism of Progesterone, Estradiol and Androstenedione in the Vascularly Separated and Isolated Hypothalamus of the Female Rhesus Monkey

In situ Subcellular Distribution and Metabolism of Progesterone, Estradiol and Androstenedione in the Vascularly Separated and Isolated Hypothalamus of the Female Rhesus Monkey

Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions

In situ Estradiol and Progestin (R5020) Localization in the Vascularly Separated and Isolated Hypothalamus of the Rhesus Monkey

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