Association of Tritium-Labelled Estradiol, Progesterone and 17&lt;i&gt;α&lt;/i&gt;-Hydroxyprogesterone with the Proteins of the Serum and Cerebrospinal Fluid in the Rhesus Monkey

Umberkoman-Wiita, B.; Kumar, T. C. Anand

doi:10.1159/000122850

Cited by 6 publications

(5 citation statements)

References 12 publications

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“…Secondly, progesterone has been implicated in changes of mood (such as premenstrual tension [11]). Since progesterone may also be bound by CBG [30,33], it is possible that these putative effects may be the result of the displacement of cortisol, which itself can affect mood [3], from the blood into the cerebral compartment. Again, no ef fect of progesterone could be demonstrated, perhaps be cause physiological levels of progesterone in the blood are small compared with those of cortisol.…”

Section: Discussionmentioning

confidence: 99%

“…To define more closely the relationship of cortisol in blood and CSF, the proportions o f 'free' and 'bound' cortisol in serum were de termined under a variety of conditions. Progesterone is also bound by CBG in the blood [30,33] and may thus alter the distribution of cortisol between the two compartments. This was studied by measuring CSF cortisol levels after serum progesterone had been raised to values similar to those found during the luteal phase of the menstrual cycle.…”

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confidence: 99%

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Factors Regulating Levels of Cortisol in Cerebrospinal Fluid of Monkeys during Acute and Chronic Hypercortisolemia

Martensz¹,

Herbert²,

Stacey³

1983

Neuroendocrinology

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Cortisol levels in the serum and cerebrospinal fluid (CSF) were studied in ovariectomized, estrogen-treated monkeys during either prolonged hypercortisolemia or the more transient effects of a bolus injection of cortisol. Control (saline-treated) animals showed the expected diurnal rhythm in serum cortisol, but proportionately more cortisol was present in the CSF when serum levels were high (i.e. in the morning). Prolonged hypercortisolemia for up to 37 days was produced by either thrice daily injections of cortisol itself or single daily injections of ACTH_1-24 in the morning. Both treatments produced disproportionately larger amounts of cortisol in the CSF than in the serum, and the CSF/serum cortisol ratio was increased. Furthermore, prolonged ACTH treatment caused a marked elevation in CSF cortisol in afternoon samples taken at 16.30 h compared with those at 10.00 h, in the absence of a similar change in serum cortisol levels. The relative importance of entry and clearance of cortisol in the CSF in these conditions was studied in several ways. ‘Free’ cortisol levels in serum (determined by equilibrium dialysis) were equal to CSF cortisol levels in control monkeys, but were less than those in the CSF of hypercortisolemic animals. Entry of cortisol into CSF after a bolus injection was rapid, but, unlike serum, CSF cortisol levels did not decline significantly over a 70-min sampling period and the delayed clearance from the CSF could account for some of the effects seen during hypercortisolemia. Neither high levels of prolactin (which is elevated together with cortisol in ‘stress’), induced by giving sulpiride, nor treatment with progesterone (which is also bound by corticosteroid binding globulin) altered the distribution of cortisol between blood and CSF. The concentrations of cortisol in the CSF therefore are regulated by factors influencing both its entry and clearance from the cerebral compartment. Neural tissues sensitive to cortisol are thus exposed to levels of this hormone that are both qualitatively and quantitatively different from those expected by direct extrapolation from serum levels.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Factors Regulating Levels of Cortisol in Cerebrospinal Fluid of Monkeys during Acute and Chronic Hypercortisolemia

Martensz¹,

Herbert²,

Stacey³

1983

Neuroendocrinology

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“…The association of tritiated testosterone ([l,2,6,7-3H]testosterone, 93-5Ci/mmol; Amersham International Ltd, Bucks) with serum proteins of untreated or Rivanol-treated antiserum or non-immune serum was studied by polyacrylamide gel electrophoresis (PAGE) (Davis, 1962) as described by Umberkoman-Wiita & Anand Kumar (1979).…”

Section: Methodsmentioning

confidence: 99%

“…4) Active immunization of an ovariectomized rhesus monkey produced an antiserum with a high degree of specificity towards testosterone. The electrophoretic profiles indicated that whilst testosterone is normally bound by a serum protein with a mobility similar to that of sex hormone binding globulin (Ritzen, French, Weddington, Nayfeh & Hansson, 1974;Umberkoman-Wiita & Anand Kumar, 1979) after immunization testosterone was as¬ sociated with the -globulin fraction, an association which was retained after treatment with Rivanol.…”

Section: Methodsmentioning

confidence: 99%

Effects of passive immunization against testosterone on the sexual activity of female rhesus monkeys

Martensz¹,

Everitt²

1982

Journal of Endocrinology

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Active immunization of an ovariectomized rhesus monkey against testosterone-3(0-carboxymethyl)oxime-bovine serum albumin produced an antiserum with a high degree of specificity towards testosterone. Passive immunization of ovariectomized, oestrogen-treated monkeys with this antiserum resulted in significant reductions in proceptive and/or receptive behaviours in the majority of animals. This effect could be reversed by treatment with 17 alpha-methyltestosterone, a steroid which showed only 6% cross-reaction with the antiserum. Passive immunization caused an increase in the binding of testosterone by the gamma-globulin fraction of serum isolated by treatment with 2-ethoxy-6,9-diaminoacridine lactate. The present findings emphasize the importance of androgens of adrenal origin in the regulation of sexual behaviour in the female rhesus monkey.

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“…The antecubital vein was used for the systemic administration of the steroid, and blood samples were drawn from the saphenous vein. Samples of clear free-flowing CSF were drawn from the cisterna magna as described (11).…”

mentioning

confidence: 99%

Pharmacokinetics of progesterone after its administration to ovariectomized rhesus monkeys by injection, infusion, or nasal spraying.

Kumar¹,

Dávid²,

Sankaranarayanan³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

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The pharmacokinetics of progesterone (dose: 10 jig per animal) were studied in blood and cerebrospinal fluid of adult ovariectomized rhesus monkeys after the administration of the steroid as an intravenous injection, intravenous infusion (duration of infusion: 10 min), or nasal spray. The bioavailability of progesterone, in terms of area under the time-concentration curve and the maximal concentration in the two body fluids, was significantly higher when the steroid was infused or sprayed intranasally than when it was injected intravenously. The clearance of the steroid from the serum, as estimated by its elimination rate constant, elimination half-life, and total body clearance, did not differ for the three methods ofadministration. These findings suggest that the bioavailability of progesterone is enhanced by extending the duration over which the steroid is delivered into the hemal circulation.Reports from our laboratories have shown that marked neuroendocrine effects leading to an impairment of ovarian (1) or testicular (2) functions occur after the intranasal spraying ofprogesterone in extremely low doses likely to be ineffective when administered by oral or systemic routes. It has been suggested (3) that these marked effects observed with low doses of the steroid administered by an unconventional route may be related to the rapid and preferential transfer of the steroid to the brain via the cerebrospinal fluid (CSF). This suggestion is based on the finding of much higher levels of progesterone in the CSF after its being sprayed intranasally in comparison with its systemic administration (4,5).Because the pharmacological effects of a drug are known to be related to its bioavailability to target tissues rather than to its administered dose, it was felt that a comparison of the pharmacokinetics of progesterone after its systemic administration and intranasal spraying would be useful in furthering our understanding of these unique, low-dose effects occurring upon administering the steroid by an unconventional method. The studies reported here were carried out to obtain such data with particular reference to the bioavailability ofprogesterone to tissues bathed by blood, CSF, or both after the administration of progesterone by three different methods: intravenous (i.v.) injection, i.v. infusion, and nasal spray (n.s.).MATERIALS AND METHODS Animals. Six healthy adult female rhesus monkeys of similar body weights (5-6.5 kg) and sizes (6) were selected from the Primate Research Facility of our institute (7). These animals consistently exhibited ovulatory menstrual cycles ofnormal duration (23-28 days) before they were ovariectomized. They were used 2 months after ovariectomy. The clinical condition of all the animals, with particular reference to their liver and renal functions, as evaluated by estimating blood or serum levels of proteins, albumin, bilirubin, alkaline phosphatase, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, urea, and creatinine were within normal values reported for th...

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Association of Tritium-Labelled Estradiol, Progesterone and 17<i>α</i>-Hydroxyprogesterone with the Proteins of the Serum and Cerebrospinal Fluid in the Rhesus Monkey

Cited by 6 publications

References 12 publications

Factors Regulating Levels of Cortisol in Cerebrospinal Fluid of Monkeys during Acute and Chronic Hypercortisolemia

Factors Regulating Levels of Cortisol in Cerebrospinal Fluid of Monkeys during Acute and Chronic Hypercortisolemia

Effects of passive immunization against testosterone on the sexual activity of female rhesus monkeys

Pharmacokinetics of progesterone after its administration to ovariectomized rhesus monkeys by injection, infusion, or nasal spraying.

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