Effects of graded doses of triiodothyronine on TSH synthesis and secretion rates in hypothyroid rats

1981 ◽  
Vol 97 (1) ◽  
pp. 74-84 ◽  
Author(s):  
Th. Lemarchand-Béraud ◽  
C. Berthier
Keyword(s):  
Fold Increase ◽  
High Plasma ◽  
Male Rats ◽  
Slight Reduction ◽  
Metabolic Clearance ◽  
Clearance Rates ◽  
Tsh Secretion ◽  
Previously Treated ◽  
Secretion Rates ◽  
Tsh Levels

Abstract. The effects of a graded low dose of T3 on plasma TSH, anterior pituitary TSH content (AP-TSH) and on TSH synthesis and secretion rates, were studied in adult male rats previously treated for 7 days with 0.01% prophylthiouracil (PTU). Pituitary TSH content, plasma T3, T4 and TSH levels were measured by RIA at 0, 6, 12, 24 h after the injection of T3 ranging from 0.1 to 0.75 μg/100 g b.w. Saline treated normal rats served as control. The 7-day PTU treated rats displayed low but still detectable thyroid hormone plasma levels; high plasma TSH levels were observed, but with no further increase after TRH injection as the AP-TSH content was depleted. Injections of T3 increased plasma T3 in proportion with the dose given. Plasma T4 remained low and there was no significant decrease in plasma TSH until doses of 0.2 μg/100 g b.w. T3 was given. Then the transient TSH depression was dose-dependent from 0.2 to 0.75 μg/100 g b.w. The AP-TSH content increased regularly from 0.2 μg/T3 onwards, overlapping the transient inhibition of TSH secretion resulting in a 3-fold increase in the AP-TSH content, suggesting a positive action of T3 on TSH synthesis. In addition, TSH response to TRH was observed at every time studied after T3 injection. Then, the different groups were injected with [125I]rTSH in order to estimate metabolic clearance rates, TSH secretion and synthesis rates. The half-life of [125I]rTSH (22 min) and its metabolism clearance rates (16 ± 0.4 ml/h/100 g b.w.) were found similar in all groups. Whereas the TSH secretion rates was highly reduced in the normal rats receiving 0.3 μg T3 (156 ± 9 vs 408 ± 22 μg/24 h in normal rats), the PTU group displayed a 3-fold increased secretion rate (1222 ± 44 μg/24 h) which was not modified by the injection of 0.1–0.2 μg T3 and decreased to 868 and 472 μg/24 h with 0.3 μg and 0.75 μg T3, respectively. TSH synthesis rates were found highly increased in the PTU group (1222 ± 44 μg/d vs 408 ± 22 μg/d in normal rats) and was neither increased nor reduced in the 7-day PTU rats receiving 0.1–0.3 μg T3 but a slight reduction was observed only in the 0.75 μg T3 group. These data show that 0.1–0.2 μg/100 g b.w. T3 changed neither TSH secretion nor its synthesis rates while 0.3 μg more or less a replacement dose inhibited TSH secretion without changing TSH synthesis rates, resulting in a AP-TSH replenishment. Therefore, no direct positive effect of low doses of T3 on TSH synthesis could be demonstrated over 24 h while higher doses are capable of inhibiting first secretion and then synthesis of TSH.

TSH SYNTHESIS AND RELEASE IN THE THYROIDECTOMIZED RAT:

1979 ◽  
Vol 92 (3) ◽  
pp. 489-501 ◽  
Author(s):  
O. Spira ◽  
A. Birkenfeld ◽  
J. Gross ◽  
A. Gordon
Keyword(s):  
Steady State ◽  
Compartmental Analysis ◽  
Fold Increase ◽  
Progressive Increase ◽  
Male Rats ◽  
Metabolic Clearance ◽  
Normal Value ◽  
Plateau Level ◽  
Tsh Levels ◽  
Stimulation Of

ABSTRACT Groups of surgically thyroidectomized (T) male rats were sacrificed at intervals during the period of 1 to 5 and 30 to 180 days after <UNK> Plasma T3, T4 and TSH levels and pituitary TSH content were measured by RIA. A drop of plasma T3 and T4 from normal to undetectable values occurred by day 3 post <UNK>. There was a progressive increase of plasma TSH from the normal value of 136 ± 14 ng/ml to 1623 ± 186 ng/ml (mean ± sem) at day 5 post T, reaching at 30 days a new plateau of 8618 ± 527 ng/ml. These levels remained unchanged up to 130 days post <UNK>. At 180 days, plasma TSH (4123 ± 991 ng/ml) fell significantly below the plateau level. Pituitary TSH content fell from the normal value of 80.9 ± 15.9 μg/mg to a nadir of 12.7 ± 1.4 μg/mg at day 4 post <UNK> and then slowly rose to 98.6 ± 5.9 μg/mg at 100 days, remaining at this level for another 30 days and finally declining significantly at 180 days post <UNK>. The rates of TSH release and synthesis were calculated using the metabolic clearance rates (MCR), determined from the curves of disappearance of injected [125I]-TSH by a non-compartmental analysis. The MCR values decreased, starting at 8 days after T, and reached about half the normal value from 30 days onwards (0.257 ± 0.03 to 0.144 ± 0.001 ml/min/100 g b.w.). The rate of TSH release was increased as early as the first day post <UNK>. A 6-fold increase was reached after 5 days and a new steady state of about 32-fold increase was attained within 1 month. TSH synthesis was also stimulated. However, it lagged behind the stimulation of the release for the first 4 days after <UNK>. The data indicate that: a) The depletion of thyroid hormones affects both synthesis and release of TSH. b) Under prolonged hypothyroidism TSH release and synthesis are in equilibrium, at a markedly enhanced rate. c) Very severe and prolonged hypothyroidism results in a decline in both pituitary and plasma TSH levels.

INDUCTION OF GOITRE BY PTU OR KClO4 IN MALE AND FEMALE RATS. EFFECT OF GONADECTOMY

1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia
Keyword(s):  
Iodine Content ◽  
High Plasma ◽  
Disc Electrophoresis ◽  
Female Rats ◽  
Male Rats ◽  
Adult Rats ◽  
Male And Female ◽  
Glucose Levels ◽  
Male And Female Rats ◽  
Tsh Levels

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.

Acute stress attenuates but does not abolish circadian rhythmicity of serum thyrotrophin and growth hormone in the rat

1996 ◽  
Vol 135 (6) ◽  
pp. 703-708 ◽  
Author(s):  
Octavi Martí ◽  
Amadeu Gavaldà ◽  
Trinidad John ◽  
Antonio Armario
Keyword(s):  
Growth Hormone ◽  
Food Intake ◽  
Acute Stress ◽  
Dark Period ◽  
Circadian Rhythmicity ◽  
Male Rats ◽  
Separate Experiment ◽  
Daily Rhythms ◽  
Tsh Secretion ◽  
Tsh Levels

Martí O, Gavaldà A, Jolín T, Armario A. Acute stress attenuates but does not abolish circadian rhythmicity of serum thyrotrophin and growth hormone in the rat. Eur J Endocrinol 1996;135:703–8. ISSN 0804–4643 The effects of acute immobilization (IMO) on daily rhythms of corticosterone, thyroid-stimulating hormone (TSH) and growth hormone (GH) were studied in adult male rats. Two hours of IMO increased serum corticosterone, this increase still being observed 3 h after finishing stress exposure. In the dark period corticosterone levels did not differ in control and IMO rats, but higher levels were observed again in the morning of the day after. Immobilization lowered serum GH and TSH levels throughout the 24-h period that followed exposure to the stressor. Such an effect was more marked in GH than in TSH. In addition, GH, but not TSH, levels were found to be reduced significantly by IMO at 08.30 h of the next day. None the less, daily rhythms of GH and TSH were still persistent and roughly similar to those of control rats. The daily rhythm of food intake was measured in a separate experiment and it was observed, as expected, that IMO reduced food intake only in the dark period of the lighting cycle. It appears therefore unlikely that IMO-induced anorexia was the major factor responsible for the inhibition of GH and TSH caused by IMO at 11.00 and 19.00 h, considering that the amount of food intake was very low and similar in control and IMO rats during this period. However, anorexia might have contributed to inhibition of GH and TSH secretion afterwards. Thus, in a third experiment we studied the contribution of IMO-induced anorexia to the changes in hormone levels observed 24 h after stress by introducing a group of pair-fed rats. It was found that IMO, but not pair-feeding, reduced TSH levels, whereas a similar reduction of GH was found in the two conditions. It might be concluded that acute stress transiently altered corticosterone secretion, the only long-lasting effect being a slight increase in its morning levels on the following stress. Immobilization also causes an inhibition of GH and TSH secretion in the rat that persists for several hours after finalization of exposure to the stressor, but daily rhythms were still apparent. It appears that the contribution of stress-induced anorexia is different in GH than in TSH. In conclusion, an acute severe stressor such as IMO, although modifying circulating levels of some hormones, particularly in the hours following exposure to the stressor, did not appear to interfere greatly with the expression of circadian rhythms of anterior pituitary hormones. Octavi Martí, Unitat de Fisiologia Animal, Facultat de Ciències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain

THE RATES OF PLASMA CORTISOL ENTRY AND CLEARANCE IN SHEEP BEFORE AND DURING THEIR EXPOSURE TO A COLD, WET ENVIRONMENT

1970 ◽  
Vol 47 (3) ◽  
pp. 273-285 ◽  
Author(s):  
B. A. PANARETTO ◽  
MARION R. VICKERY
Keyword(s):  
Rectal Temperature ◽  
Plasma Cortisol ◽  
High Plasma ◽  
Separate Experiment ◽  
Terminal Phase ◽  
Metabolic Clearance ◽  
Clearance Rates ◽  
Entry Rate ◽  
Severe Hypothermia ◽  
Transitory Effect

SUMMARY Plasma cortisol concentrations and entry rates increased greatly when nine shorn sheep were exposed to cold, wet conditions for periods up to 70 hr. The average entry rate in four of the cold-stressed animals before their rectal temperatures began to fall was 25 μg./min., approximately three to four times greater than in the same sheep before exposure (7·7 μg./min.). The metabolic clearance rates at this time remained unchanged. Plasma cortisol concentration began to increase about 2–3 hr. before the sheeps' rectal temperatures began to fall. The increase continued until concentrations of 100–200 μg./1. were reached after the sheeps' rectal temperature had fallen. Cortisol entry increased at this time to what may probably be maximal or near maximal rates in the sheep (about 150–200 μg./min.). Lowered clearance did not appear to contribute substantially to increased plasma cortisol concentrations at rectal temperatures above 34°. Since clearance rates did not begin to fall rapidly until rectal temperature fell below about 34°, cortisol entry during the terminal phase of hypothermia, approximately 76 μg./min., was very much less than the observed maximum and the high plasma cortisol concentrations measured during this period were residual and sustained by lowered clearance rates. The adrenal cortices and livers of the sheep after severe hypothermia were heavily infiltrated with fat. The effects of shearing alone, studied in a separate experiment, had a transitory effect since plasma cortisol concentrations and entry rates had returned to near their pre-shearing levels by about 27 hr.

Heterogeneity of rat FSH by chromatofocusing: studies on serum FSH, hormone released in vitro and metabolic clearance rates of its various forms [ill]

1985 ◽  
Vol 105 (1) ◽  
pp. 29-37 ◽  
Author(s):  
W. F. P. Blum ◽  
D. Gupta
Keyword(s):  
Molecular Size ◽  
Male Rats ◽  
Metabolic Clearance ◽  
Clearance Rates ◽  
Charged Species ◽  
Rat Pituitary ◽  
Isoelectric Points ◽  
Exclusion Chromatography ◽  
Pituitary Glands

ABSTRACT Rat pituitary FSH was fractionated by chromatofocusing between pH 6 and 3. Ten components were resolved having apparent isoelectric points between 3·1 and 5·1. A comparative study of pituitary FSH and FSH secreted in vitro by quartered pituitary glands in the presence and in the absence of gonadotrophin-releasing hormone (GnRH) revealed similar patterns of charged species of intracellular and released FSH. Although GnRH increased FSH secretion about fourfold, no influence on the pattern of charged species was observed. Utilizing exclusion chromatography and chromatofocusing, pituitary FSH was compared to serum FSH which had been extracted by immunoaffinity chromatography. The results demonstrate for serum FSH a larger molecular size and a relative shift to more acidic components. Metabolic clearance rates of eight FSH components separated by chromato-focusing were measured in adult male rats. Half-lives varied between 13 min and several hours. A correlation existed between decrease of isoelectric points and decrease of metabolic clearance rates. These findings suggest that (1) all hypophysial FSH components are secreted into the circulation at similar rates and (2) the more acidic FSH components which appear to contain increased sialic acid, have a longer circulatory half-life and are more abundant in serum. It is concluded that sialylation may be involved in modulating serum FSH levels. J. Endocr. (1985) 105, 29–37

A COMPARISON OF CHANGES IN THE PERIPHERAL PLASMA CONCENTRATIONS OF LUTEINIZING HORMONE AND FOLLICLESTIMULATING HORMONE IN THE RAT

1975 ◽  
Vol 65 (3) ◽  
pp. 389-397 ◽  
Author(s):  
K. BROWN-GRANT ◽  
FENELLA GREIG
Keyword(s):  
Plasma Concentrations ◽  
Fold Increase ◽  
Early Response ◽  
Female Rats ◽  
Male Rats ◽  
Postnatal Life ◽  
Experimental Conditions ◽  
Releasing Factors ◽  
Secretion Rates ◽  
Sustained Increase

SUMMARY Plasma FSH concentrations in rats have been determined by radioimmunoassay under a variety of experimental conditions to see whether any evidence could be obtained of an acute divergence in LH and FSH secretion rates which would support the idea of separate, specific hypothalamic releasing factors for these two hormones. During the normal ovarian cycle and after the administration of progesterone to female rats on the morning of the day of pro-oestrus increased secretion of both LH and FSH began simultaneously but FSH concentrations were later maintained or increased slightly while LH concentrations were falling. During early pregnancy FSH concentrations were higher than at the corresponding stage of the cycle at a time when LH concentrations had been shown to be lower. Progesterone injected at the dioestrous stage of the cycle reduced both LH and FSH concentrations though the effect on LH was more marked. After ovariectomy at any stage of the oestrous cycle or on day 4 of pregnancy there was a rapid and significant increase in plasma FSH concentration which was quite different from the delayed increase in LH concentration observed in these animals. In contrast, the early increase in FSH concentration in male rats after castration was less than the increase in LH concentration. The final FSH concentration in castrated males was only about four times the basal level in contrast to the 10- to 15-fold increase in LH in males and both LH and FSH in females. Anovulatory adult females that had received 1·25 mg of testosterone propionate on day 4 of postnatal life showed the rapid and sustained increase in plasma FSH after ovariectomy that was seen in normal females. None of these results strongly support the idea that separate and specific hypothalamic releasing factors for LH or FSH are secreted in the rat although the differences in the early response to gonadectomy could be explained on this basis.

NEUROTRANSMITTER CONTROL OF THYROTROPHIN SECRETION IN HYPOTHYROID RATS

1978 ◽  
Vol 89 (1) ◽  
pp. 100-107 ◽  
Author(s):  
P. T. Männistö ◽  
T. Ranta
Keyword(s):  
Dopaminergic System ◽  
Tap Water ◽  
Male Rats ◽  
Noradrenergic System ◽  
High Dose ◽  
Tsh Secretion ◽  
Pre Treatment ◽  
Open Question ◽  
Serum Tsh ◽  
Tsh Levels

ABSTRACT The effect of drugs modifying dopaminergic, noradrenergic and serotonergic systems on the serum TSH levels was studied in the male rats made hypothyroid by giving 10 mg/l of propylthiouracil in tap water for 4 days. Apomorphine (2.5 mg/kg, given once −30 min before sacrifice; or four times −120, 90, 60 and 30 min before sacrifice), bromocryptine (10 and 20 mg/kg, 2 h before sacrifice) and piribedil (50 and 100 mg/kg, 4 h) decreased the serum TSH concentrations. The effect of a single dose of apomorphine (2.5 mg/kg, 30 min before sacrifice) was partially reversed by a pimozide pre-treatment (2.5 mg/kg, 2 h). Clonidine (1 mg/kg but not 0.01 or 0.1 mg/kg, 2 h before sacrifice) further elevated the high TSH levels whereas α-methyl-p-tyrosine (300 mg/kg, 2 h), phenoxybenzamine (50 mg/kg, 2 h) and diethyldithiocarbamate (300 mg/kg, 2 h) significantly decreased TSH secretion. The effect of clonidine (1 mg/kg, 2 h) was partially antagonized by phenoxybenzamine (20 mg/kg, 2 h). A high dose of 5-HTP (300 mg/kg, 2 h) increased serum TSH concentrations whereas p-chlorophenylalanine (100 mg/kg, 2 h) decreased it. When both drugs were given together, the serum TSH levels did not change. L-tryptophan (100–300 mg/kg, 2 h) uniformly decreased the serum TSH concentrations in all experiments. It is concluded that in the hypothyroid rats, the secretion of TSH is inhibited by dopaminergic system, and stimulated by noradrenergic system. The effect of 5-HT pathways remained an open question.

Effect of amiodarone on non-deiodinative pathway of thyroid hormone metabolism

1990 ◽  
Vol 122 (2) ◽  
pp. 249-254 ◽  
Author(s):  
Ram Kannan ◽  
Inder J. Chopra ◽  
Murad Ookhtens ◽  
Bramah N. Singh
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Area Under The Curve ◽  
Fold Increase ◽  
Molar Ratio ◽  
Metabolic Clearance ◽  
Clearance Rates ◽  
Experimental Conditions ◽  
Daily Production ◽  
Thyroid Hormone Metabolism

Abstract Amiodarone, an iodine containing anti-arrhythmic drug, causes a significant decrease in molar ratio of daily production rates of T3 and T4 from 0.75 in controls to 0.36 in amiodarone-treated rabbits. A model was constructed from the above data which showed that metabolism of T4 via non-deiodinative pathways (e.g. tetraiodothyroacetic acid and/or conjugates) increased from 29% in untreated controls to 66% in amiodarone-treated rabbits. In this study, we have examined the metbolic clearance rate of tetraiodothyroacetic acid in rabbits given amiodarone (20 mg·kg−1·day−1 ip for 3 weeks) or saline (controls). Serum amiodarone and desethylamiodarone levels under the above experimental conditions were 0.20±0.067 and 0.17±0.058 mg/l, respectively, which were in the near-therapeutic range observed in humans. Control and amiodarone-treated rabbits were administered [125I]-tetraiodothyroacetic acid (10 μCi/rabbit) iv and blood was collected at 0.5, 1, 2, 4, 6, 10, 32 and 48 h. Serum tetraiodothyroacetic acid radioactivity was determined by trichloroacetic acid precipitation and ethanol extraction and metabolic clearance rates were calculated from the area under the curve of computer fits to tetraiodothyroacetic acid radioactivity data. Amiodarone treatment decreased metabolic clearance rates significantly from 0.107 ± 0.008 in controls to 0.074 ± 0.009 1/day in amiodarone-treated rabbits (p<0.05). However, when expressed per unit body weight (1·day−1·kg−1), the metabolic clearance rates were not significantly different between the controls and amiodarone-treated rabbits. The terminal serum elimination half-life in the two groups were similar (32.0 ± 6.7 h in controls vs 49.2 ± 12.4 h in amiodarone-treated). Our data suggest that a modest decrease in clearance rate and an increased production rate could result in an increase in serum tetraiodothyroacetic acid levels which may contribute to the reduction in 5'-monodeiodination of iodothyronines documented previously in amiodarone-treated animals. The marginal decrease in metabolic clearance rate of tetraiodothyroacetic acid found in this study suggests that the two-fold increase in the conversion of T4 metabolism to non-deiodinated metabolites/conjugates in amiodarone-treated rabbits results predominantly from an increase in production rate of tetraiodothyroacetic acid.

DUAL ACTION OF ADRENERGIC SYSTEM ON THE REGULATION OF THYROTROPHIN SECRETION IN THE MALE RAT

1979 ◽  
Vol 90 (2) ◽  
pp. 249-258 ◽  
Author(s):  
Pekka Männistö ◽  
Tapio Ranta ◽  
Jouko Tuomisto
Keyword(s):  
Cold Exposure ◽  
Male Rats ◽  
Male Rat ◽  
Adrenergic System ◽  
Inhibitory Function ◽  
Adrenergic Activity ◽  
Tsh Secretion ◽  
Dual Action ◽  
Serum Tsh ◽  
Tsh Levels

ABSTRACT The effect of graded doses of drugs modifying adrenergic activity on basal and cold-stimulated TSH secretion was studied in male rats, ±-Methyl-p-tyrosine (±MPT) (16 h before 30 min cold-exposure), phenoxybenzamine (1 h), Ca-fusarate (1 h) and diethyldithiocarbamate (DDC) (1 and 18 h) dose-dependently depressed the cold-stimulated TSH secretion. The effect of reserpine (24 h) was not significant. Clonidine (1 h), dihydroxyphenylserine (DOPS) (1 h), noradrenaline (NA) (1 h), and l-Dopa (1 h) were also effective in decreasing serum TSH levels, but dopamine (DA) (ad 2 mg/kg, 1 h) had no effect. Basal TSH levels were also decreased by various doses of clonidine, DOPS and NA, given ip 1 h before sacrifice. Clonidine (1 mg/kg), NA (1 mg/kg), DA (2 mg/kg), ±MPT (300 mg/kg), phenoxybenzamine (2 or 20 mg/kg), Ca-fusarate (50 mg/kg) or l-Dopa (200 mg/kg) did not modify the TRH-induced TSH response. These results cannot be explained by assuming only a stimulatory function for the adrenergic system on the secretion of TSH in the rat. The site of the possible inhibitory function of noradrenaline in the control of TSH cannot be deduced from these results, but various possibilities are discussed.

Contribution of dehydroepiandrosterone and its sulfate to estradiol in baboon pregnancy.

1978 ◽  
Vol 235 (1) ◽  
pp. E78
Author(s):  
H A Schut ◽  
G J Pepe ◽  
R A Chez ◽  
J D Townsley
Keyword(s):  
Intravenous Infusion ◽  
Serum Levels ◽  
Metabolic Clearance ◽  
Serum Estradiol ◽  
Clearance Rates ◽  
Production Rates ◽  
Efficient Conversion ◽  
Papio Papio ◽  
Secretion Rates ◽  
Low Serum

The metabolic clearance rates (MCR), conversion ratios (C), interconversion (rho), production rates (PR), secretion rates (SR), and relative contributions of maternal dehydroepiandrosterone (D) and D-sulfate (DS) to serum estradiol (E2) were determined in five pregnant baboons (Papio papio; 154-167 days gestation, term = 184 days) by constant intravenous infusion of [3H]DS and [14C]D. MCR-D (mean +/- SE) was greater (39.2 +/- 3.3 1/day.kg, P less than 0.001) than MCR-DS (3.1 +/- 0.3 1/day.kg). Because C-D leads to DS (5.460 +/- 0.461) exceeded (P less than 0.001) C-DS leads to (0.006 +/- 0.001), rho-DS leads to DS was greater (42.5% +/- 3.0%, P less than 0.001) than rho-DS leads to D (7.8 +/- 1.0%). C-D leads to E2 was greater (0.256 +/- 0.040) than C-DS leads to E2 (0.002 +/- 0.000). Using these values and serum levels of D (2.46 microgram/100 ml) and DS (18.9 microgram/100 ml) reported previously, SR and PR of D and DS were calculated. Of the total D produced (11.5 microgram/min), 98% was secreted, whereas only 32% of DS produced (7.1 microgram/min) was due to secretion. Using the serum D and DS levels and their conversion to E2, it was calculated that 89.7% of serum E2 was formed directly from D, 4.4% from D via DS, 1.8% from DS directly, and 4.1% from DS via D. It is concluded that, in spite of the low serum D level resulting from a high MCR, the large SR-D and more efficient conversion of D to E2 makes D, and not DS, the major circulating estrogen precursor in late baboon pregnancy.

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