Cortisol production and metabolism in the late gestation rhesus monkey fetus

B. F. Mitchell, M. Seron-Ferre, David Hess, R. B. Jaffe

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Cortisol metabolism was studied in the pregnant rhesus monkey and her fetus at 135-140 days gestation using 5 long term catheterized fetal preparations. Two different isotope methods were used. The first method, employing simultaneous constant infusions of [3H]cortisol into the fetus and [14C]cortisol into the mother, demonstrated that the fetus had a significantly higher cortisol production rate than did the mother when expressed in terms of body weight (8.3 ± 1.6 vs. 3.4 ± 0.6 mg/kg · day). The fetus also had a higher cortisol MCR (76.7 ± 13.9 vs. 20.4 ± 5.4 liters/kg · day). The fetal adrenal secretion rate at this gestational age was not significantly different from the maternal rate (5.3 ± 1.9 vs. 3.2 ± 0.6 mg/kg · day, respectively). There was extensive transfer of cortisol in both directions across the placenta, with no net gain in cortisol for the fetus. However, at any particular time, 43.5% of the cortisol in the fetal circulation was derived from maternal secretion. In addition, 71.8% of fetal cortisone, a major metabolite and possible precursor of cortisol, was derived from maternal cortisol. The 3H to 14C ratios of cortisol and cortisone in the amniotic fluid and fetal and maternal circulations suggest that a large portion of amniotic fluid cortisol arises either directly from maternal cortisol or from cortisone in any of the three compartments. A bolus injection method, with computer analysis of the disappearance curve, also was used to estimate fetal cortisol production rate (5.8 ± 0.8 mg/kg · day) and MCR (86.3 ± 5.2 liters/kg · day). These values were not significantly different from those determined in the constant infusion experiments. The fetal cortisol production rate was not significantly different from that in a group of 7 infant monkeys during the first week of life (5.6 ± 1.2 mg/kg · day). Both the fetal and infant cortisol production rates were higher than those in a group of 5 healthy adult female monkeys (1.9 ± 0.7 mg/kg · day). Also, the fetal cortisol MCR was greater than that in the infant (27.1 ± 3.0 liters/kg · day) or the adult group (11.9 ± 1.8 liters/kg · day). The infant MCR was significantly greater than that in the adult. Analysis of the relative amounts of cortisone appearing after the bolus injection indicated that oxidation of cortisol to cortisone was a major method of clearance in the fetus and infant but was of much less importance in the nonpregnant adult. These data demonstrate that the late gestation fetal rhesus monkey actively secretes significant amounts of cortisol. The total amounts of cortisol produced in the fetus and infant are greater than that in the mother when expressed on the basis of body weight. Cortisol is cleared very rapidly from the fetus, due in large part to extensive feto-maternal transfer. There also is considerable oxidation of cortisol to cortisone in the fetus, and this metabolic pathway is preserved in the infant monkey. The regulation of fetal adrenal secretion, placental transfer, and interconversion of cortisol and cortisone are important factors in the control of fetal glucocorticoid activity.

Original languageEnglish (US)
Pages (from-to)916-924
Number of pages9
JournalEndocrinology
Volume108
Issue number3
StatePublished - 1981
Externally publishedYes

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Macaca mulatta
Hydrocortisone
Fetus
Pregnancy
Cortisone
Mothers
Haplorhini
Amniotic Fluid
Body Weight
Fetal Movement
Injections

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Mitchell, B. F., Seron-Ferre, M., Hess, D., & Jaffe, R. B. (1981). Cortisol production and metabolism in the late gestation rhesus monkey fetus. Endocrinology, 108(3), 916-924.

Cortisol production and metabolism in the late gestation rhesus monkey fetus. / Mitchell, B. F.; Seron-Ferre, M.; Hess, David; Jaffe, R. B.

In: Endocrinology, Vol. 108, No. 3, 1981, p. 916-924.

Research output: Contribution to journalArticle

Mitchell, BF, Seron-Ferre, M, Hess, D & Jaffe, RB 1981, 'Cortisol production and metabolism in the late gestation rhesus monkey fetus', Endocrinology, vol. 108, no. 3, pp. 916-924.
Mitchell BF, Seron-Ferre M, Hess D, Jaffe RB. Cortisol production and metabolism in the late gestation rhesus monkey fetus. Endocrinology. 1981;108(3):916-924.
Mitchell, B. F. ; Seron-Ferre, M. ; Hess, David ; Jaffe, R. B. / Cortisol production and metabolism in the late gestation rhesus monkey fetus. In: Endocrinology. 1981 ; Vol. 108, No. 3. pp. 916-924.
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N2 - Cortisol metabolism was studied in the pregnant rhesus monkey and her fetus at 135-140 days gestation using 5 long term catheterized fetal preparations. Two different isotope methods were used. The first method, employing simultaneous constant infusions of [3H]cortisol into the fetus and [14C]cortisol into the mother, demonstrated that the fetus had a significantly higher cortisol production rate than did the mother when expressed in terms of body weight (8.3 ± 1.6 vs. 3.4 ± 0.6 mg/kg · day). The fetus also had a higher cortisol MCR (76.7 ± 13.9 vs. 20.4 ± 5.4 liters/kg · day). The fetal adrenal secretion rate at this gestational age was not significantly different from the maternal rate (5.3 ± 1.9 vs. 3.2 ± 0.6 mg/kg · day, respectively). There was extensive transfer of cortisol in both directions across the placenta, with no net gain in cortisol for the fetus. However, at any particular time, 43.5% of the cortisol in the fetal circulation was derived from maternal secretion. In addition, 71.8% of fetal cortisone, a major metabolite and possible precursor of cortisol, was derived from maternal cortisol. The 3H to 14C ratios of cortisol and cortisone in the amniotic fluid and fetal and maternal circulations suggest that a large portion of amniotic fluid cortisol arises either directly from maternal cortisol or from cortisone in any of the three compartments. A bolus injection method, with computer analysis of the disappearance curve, also was used to estimate fetal cortisol production rate (5.8 ± 0.8 mg/kg · day) and MCR (86.3 ± 5.2 liters/kg · day). These values were not significantly different from those determined in the constant infusion experiments. The fetal cortisol production rate was not significantly different from that in a group of 7 infant monkeys during the first week of life (5.6 ± 1.2 mg/kg · day). Both the fetal and infant cortisol production rates were higher than those in a group of 5 healthy adult female monkeys (1.9 ± 0.7 mg/kg · day). Also, the fetal cortisol MCR was greater than that in the infant (27.1 ± 3.0 liters/kg · day) or the adult group (11.9 ± 1.8 liters/kg · day). The infant MCR was significantly greater than that in the adult. Analysis of the relative amounts of cortisone appearing after the bolus injection indicated that oxidation of cortisol to cortisone was a major method of clearance in the fetus and infant but was of much less importance in the nonpregnant adult. These data demonstrate that the late gestation fetal rhesus monkey actively secretes significant amounts of cortisol. The total amounts of cortisol produced in the fetus and infant are greater than that in the mother when expressed on the basis of body weight. Cortisol is cleared very rapidly from the fetus, due in large part to extensive feto-maternal transfer. There also is considerable oxidation of cortisol to cortisone in the fetus, and this metabolic pathway is preserved in the infant monkey. The regulation of fetal adrenal secretion, placental transfer, and interconversion of cortisol and cortisone are important factors in the control of fetal glucocorticoid activity.

AB - Cortisol metabolism was studied in the pregnant rhesus monkey and her fetus at 135-140 days gestation using 5 long term catheterized fetal preparations. Two different isotope methods were used. The first method, employing simultaneous constant infusions of [3H]cortisol into the fetus and [14C]cortisol into the mother, demonstrated that the fetus had a significantly higher cortisol production rate than did the mother when expressed in terms of body weight (8.3 ± 1.6 vs. 3.4 ± 0.6 mg/kg · day). The fetus also had a higher cortisol MCR (76.7 ± 13.9 vs. 20.4 ± 5.4 liters/kg · day). The fetal adrenal secretion rate at this gestational age was not significantly different from the maternal rate (5.3 ± 1.9 vs. 3.2 ± 0.6 mg/kg · day, respectively). There was extensive transfer of cortisol in both directions across the placenta, with no net gain in cortisol for the fetus. However, at any particular time, 43.5% of the cortisol in the fetal circulation was derived from maternal secretion. In addition, 71.8% of fetal cortisone, a major metabolite and possible precursor of cortisol, was derived from maternal cortisol. The 3H to 14C ratios of cortisol and cortisone in the amniotic fluid and fetal and maternal circulations suggest that a large portion of amniotic fluid cortisol arises either directly from maternal cortisol or from cortisone in any of the three compartments. A bolus injection method, with computer analysis of the disappearance curve, also was used to estimate fetal cortisol production rate (5.8 ± 0.8 mg/kg · day) and MCR (86.3 ± 5.2 liters/kg · day). These values were not significantly different from those determined in the constant infusion experiments. The fetal cortisol production rate was not significantly different from that in a group of 7 infant monkeys during the first week of life (5.6 ± 1.2 mg/kg · day). Both the fetal and infant cortisol production rates were higher than those in a group of 5 healthy adult female monkeys (1.9 ± 0.7 mg/kg · day). Also, the fetal cortisol MCR was greater than that in the infant (27.1 ± 3.0 liters/kg · day) or the adult group (11.9 ± 1.8 liters/kg · day). The infant MCR was significantly greater than that in the adult. Analysis of the relative amounts of cortisone appearing after the bolus injection indicated that oxidation of cortisol to cortisone was a major method of clearance in the fetus and infant but was of much less importance in the nonpregnant adult. These data demonstrate that the late gestation fetal rhesus monkey actively secretes significant amounts of cortisol. The total amounts of cortisol produced in the fetus and infant are greater than that in the mother when expressed on the basis of body weight. Cortisol is cleared very rapidly from the fetus, due in large part to extensive feto-maternal transfer. There also is considerable oxidation of cortisol to cortisone in the fetus, and this metabolic pathway is preserved in the infant monkey. The regulation of fetal adrenal secretion, placental transfer, and interconversion of cortisol and cortisone are important factors in the control of fetal glucocorticoid activity.

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