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Biomedical subjects

W Wuttke

Publications and source records attributed to W Wuttke.

At least 145 records · Page 8Linked to original sources
PubMed1990

[CA-125 serum level in early pregnancy follow hMG/hCG stimulated and unstimulated cycles].

The CA-125-antigen could not only be identified in the epithelium of serous ovarian carcinoma, but also in the regular surface epithelium of the endometrium, the decidua and the peritoneum. The aim of this study was, to examine the pattern of CA-125 in the serum of women at early stages of pregnancy, after hMG/hCG-stimulation and subsequent insemination, IVF or GIFT. In particular, it was differentiated between simple or twin pregnancies, ovarian hyperstimulation syndrome and mole pregnancies. 16 patients, who spontaneously became pregnant after cyclus-monitoring, served as a control group. Among the total of 77 patients, 16 women with single pregnancies without stimulation showed an increase of CA-125 values to maximum amounts of 42.9 +/- 18.8 U/ml in the 8th week. 21 patients with single pregnancies after hMG/hCG-treatment and IVF, exhibited maximums of 97.5 +/- 66.8 U/ml in the 6th week, in cases of twins (n = 10) of 216.8 +/- 85.1 U/ml in the 7th week. Considering the group with the hMG/hCG-stimulation and following insemination (n = 20), maximum values of 91.4 +/- 57.3 U/ml were found in the 6th week, just as in the IVF-group. In cases of ovarian hyperstimulation syndrome (n = 5) as well as in such of a mole pregnancy (n = 5), drastically elevated values of 9519 and 1496 U/ml respectively, have been demonstrated. The decidua is regarded as a presumable source of high antigen levels in normal pregnancy, while the peritoneum is assumed to be such as for the ovarian hyperstimulation syndrome. Concerning mole pregnancy, the antigen levels could possibly emerge from the amniotic fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗
PubMed1990

A norepinephrine-dependent mechanism in the preoptic/anterior hypothalamic area but not in the mediobasal hypothalamus is involved in the regulation of the gonadotropin-releasing hormone pulse generator in ovariectomized rats.

Pulsatile gonadotropin secretion from the pituitary is dependent upon the gonadotropin-releasing hormone (Gn-RH) pulse generator producing intermittent release of the neuropeptide into the portal vessels. Various neurotransmitters seem to be involved in the regulation of pulsatile Gn-RH release. The present study was an attempt to determine in vivo the temporal relation of preoptic/anterior hypothalamic area (PO/AH) norepinephrine (NE) release and pulsatile luteinizing hormone (LH) secretion in ovariectomized rats. To assess whether NE acts in the PO/AH to maintain pulsatile Gn-RH release, we applied locally an alpha 1-receptor antagonist into this structure. Push-pull cannulae (PPC) were implanted into the PO/AH of ovariectomized rats. The contralateral, not PPC-implanted PO/AH was lesioned electrochemically. Another group of ovariectomized rats was implanted with a PPC into the mediobasal hypothalamus. Two experiments were performed: (1) To determine whether the PO/AH or the mediobasal hypothalamus is the site where NE exerts its stimulatory effect on LH secretion, we applied doxazosine, a new specific alpha 1-receptor antagonist, locally into these structures by means of PPC. The effect of this adrenergic drug on the Gn-RH pulse generator was examined by measuring blood LH levels. (2) To study the temporal relation between in vivo release rates of NE and amine metabolites in the preoptic area and pulsatile pituitary LH secretion, preoptic perfusates and blood samples were collected at 5-min intervals. Brain perfusates were subjected to high-performance liquid chromatography-electrochemical analysis. In blood samples LH concentrations were determined.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Effects of oxytocin on in vitro steroid release of midstage small and large porcine luteal cells.

Previously, we have demonstrated an inhibitory effect of oxytocin (OXT) on progesterone (P) and androstenedione (A) release of porcine luteal cell cultures. The present study examines whether OXT modulates P, A, or estradiol (E2) release of so-called small luteal cells (SLC) or of granulosa-derived large luteal cells (LLC). To ensure clean Percoll-gradient separation of the 2 cell types, corpora lutea not older than 6 days were used. SLC, but not LLC, responded to human (h)CG (6 ng/ml) with increased P and A, but not E2, release. When OXT was added to the culture system, both basal as well as hCG-stimulated P release of SLC, but not of LLC, were dose dependently reduced. In contrast, E2 production of SLC and LLC was significantly stimulated by OXT whereas A release of SLC cultures, but not of LLC, was inhibited in response to OXT. In the presence of a specific OXT-antagonist, this inhibitory effect of OXT on P release was abolished, indicating a specific receptor-mediated effect of OXT on porcine luteal cells. When E2 was added to the culture medium, a dose-dependent stimulatory effect on P release of SLC was demonstrated. The presence of the E2 receptor antagonist monohydroxy-tamoxifen in the culture system prevented the E2-induced increase of P release of SLC. E2 was able to counteract dose dependently the OXT-induced inhibition of P release in SLC cultures. These results suggest that OXT may have a dual function in young corpora lutea. The reduction of P and A production can be interpreted as a luteolytic effect of OXT. The simultaneous increase of E2 production, however, may also point to an indirect luteotropic effect since E2 was shown to stimulate luteal P release and to counteract OXT-induced inhibition of P release excessively.

Androstenedione↗
PubMed1990

Release and effects of oxytocin on estradiol and progesterone secretion in porcine corpora lutea as measured by an in vivo microdialysis system.

Individual corpora lutea (CL) of Göttinger miniature pigs were implanted with an in vivo microdialysis system. This system functions like an artificial capillary, allowing diffusion of intraluteally secreted substances into the lumen of the dialysis system and administration of hormones into individual CL and simultaneous measurement of the response. After surgery the sows are fully awake and unrestrained. In the present study the in vivo release rates and secretion dynamics of progesterone (P) and oxytocin (OXT) were investigated. The dialysis system was implanted at day 2-4 of the estrous cycle, and dialysis experiments were performed throughout the next 3 days. Fractions were collected at 30 min intervals, and the concentrations of P and OXT were measured by RIA. Three major observations were made: Spontaneous intraluteal secretion of P and OXT occurred in a pulsatile manner. OXT secretion episodes in individual CL often coincide, indicating a simultaneous release from many CL of one ovary but also from the CL located in the contralateral ovary. OXT episodes also often coincide with P pulses; statistical evaluation revealed a significant correlation between P and OXT secretion. Intraluteal application of OXT stimulated luteal P and estradiol (E2) release in a dose-dependent manner. E2 added to the perfusates was also stimulatory to P release. The stimulation of P release by OXT could be antagonized by prior treatment of the CL with tamoxifen. We demonstrate for the first time in vivo the secretion of OXT from porcine CL. The microdialysis system enabled us to collect samples at the site of steroid and peptide release, i.e. within the intact luteal tissue. Our results suggest a stimulatory effect of OXT on P release from young and middle-aged CL and are in marked contrast to the previously demonstrated inhibitory effect of OXT on P release when luteal cells were cultured in vitro. A possible explanation for this apparent discrepancy is that OXT stimulates intraluteal release of E2, which is a powerful P releasing hormone, overcoming the direct inhibitory effect of OXT. This suggestion is substantiated by the observation that E2, when added to the perfusion medium, indeed stimulated P release.

Animals↗
PubMed1989

In vivo demonstration of a paracrine, inhibitory action of Met-enkephalin on adrenomedullary catecholamine release in the rat.

The present study was an attempt to assess the inhibitory effect of methionine-enkephalin (Met-Enk) on adrenal catecholamine release under in vivo conditions employing a microdialysis system. One adrenal gland of intact male rats was implanted with a microdialysis system. One day after surgery, the adrenal dialysis system was connected to a perfusion pump and Ringer solution or a Ringer solution containing Met-Enk, naloxone (Nal), or a combination of Met-Enk and Nal was used for dialysis; dialysate fractions were collected at 5-min intervals. Catecholamine secretion was stimulated by an iv injection of 1.4 mumol (200 micrograms) acetylcholine (Ach). Met-Enk-immunoreactive material in adrenal medulla extracts and dialysate fractions was analyzed by reverse phase HPLC combined with Met-Enk RIA. Under resting conditions, adrenal release rates of norepinephrine and epinephrine into the Ringer solution were constant. After Ach application secretion of both catecholamines increased about 2.7-fold. Within 10 min after the injection, catecholamine levels returned to baseline levels. Intra-adrenal application of Met-Enk reduced Ach-stimulated epinephrine, but not norepinephrine, secretion significantly; application of Nal did not affect Ach-stimulated catecholamine secretion in the initial fraction after Ach injection, but significantly prolonged amine secretion after the cholinergic stimulus. Application of Nal followed by a combined application of Met-Enk and Nal was without an effect on the amount of catecholamines released in the initial fraction after Ach injection compared to that in the control group. Thus, naloxone prevented the inhibitory effect of Met-Enk on Ach-stimulated CA release. HPLC analysis of adrenal medulla extracts followed by Met-Enk RIA revealed that several forms of Met-Enk are present in chromaffin cells, whereas in adrenal dialysates only one, albeit broad, signal of Met-Enk immunoreactivity was detectable. We demonstrate in vivo a paracrine or autocrine action of Met-Enk on Ach-stimulated catecholamine release by applying the peptide directly into the adrenal gland via a microdialysis system. We conclude that neuropeptides endogenous to the adrenal gland not only reduce the amplitude of catecholamine secretion in response to an Ach stimulus but, in addition, modulate the duration of catecholamine secretion. This is demonstrated by a prolonged catecholamine secretion if opiate receptors are blocked by Nal.

Adrenal Medulla↗
PubMed1989

Inhibin production by porcine granulosa and luteal cells: development and biological validation of a RIA.

We describe the development and biological validation of a radioimmunoassay for immuno- and bioactive porcine inhibin. A synthetic 1-32 porcine inhibin peptide was used to raise an antiserum and Tyr-1-32 peptide as tracer. As standard we employed porcine follicular fluid calibrated with the 1-32 alpha-inhibin. Medium obtained from serum-free cultured porcine granulosa cells was chromatographed on Superose S-12 and Mono-Q. Resulting fractions were analysed for inhibin bio- and immunoreactivity. It is shown that granulosa cells produce at least two types of bioactive inhibins, one being also immunoactive in our RIA. We studied secretion of immunoreactive inhibin from porcine ovarian cells under various conditions: Inhibin secretion from mature and immature granulosa cells can be stimulated by FSH, whereas hCG enhances inhibin secretion only from mature granulosa cells. During extended time of culture, the capability of granulosa cells to secrete inhibin is reduced. In contrast, progesterone secretion from these cells increases; this is due to spontaneous functional luteinization. This assumption is supported by the low inhibin secretion of luteal cells in comparison to granulosa cells. Intracellular inhibin content in luteal cells is below detection limit of the RIA, whereas granulosa cells contain readily detectable amounts of this hormone.

Animals↗
PubMed1988

In vivo release rates of substance P in the preoptic/anterior hypothalamic area of ovariectomized and ovariectomized estrogen-primed rats: correlation with luteinizing hormone and prolactin levels.

Push-pull cannulae were implanted into the preoptic/anterior hypothalamic area (POA) of ovariectomized (OVX) rats. After recovery animals were treated with estradiol (E2) or corn oil and they were perfused 3 days later. Substance P (SP) concentrations were measured in 15 min perfusate fractions, blood samples were taken at similar intervals. SP concentration in POA perfusates were readily measurable. Following estrogen priming SP release increased significantly each afternoon prior to the estrogen induced prolactin and luteinizing hormone (LH) surges. No such increase of SP release was observed in OVX rats with constant LH and prolactin levels throughout the day. Mean SP rates in OVX rats were significantly higher in comparison to OVX estrogen-primed rats. These results indicate that SP may be involved in the feedback mechanisms of estrogen on prolactin and LH release. Authenticity of SP in POA perfusates was made probable by high-performance liquid chromatography (HPLC) where synthetic SP eluted at the same retention time as the signal measured in push-pull perfusates.

Animals↗
PubMed1988

Influence of different dietary proteins on plasma growth hormone in rats.

Dietary casein, compared to vegetable protein, causes hypercholesterolemia in some animal species. This may be associated with a change of hormonal status. Among others, GH has an important impact on cholesterol metabolism; GH deficiency results in hypercholesterolemia. This paper shows that the rhythmic variation of GH levels in rats is differently affected by different dietary proteins. Within a 4-h observation period overall mean values and integrated areas under the GH levels plotted against time are higher with casein as compared to soy protein. Secretory GH peak values are lower than reported before for chow-fed rats. These observations support the idea that different dietary proteins cause a different endocrine response. As GH levels are higher with casein, while lower levels would be expected to be associated with hypercholesterolemia, the observed differences are obviously of less relevance for the expression of casein-induced hypercholesterolemia.

Animals↗
PubMed1988

Age-related alterations in pulsatile luteinizing hormone release: effects of long-term ovariectomy, repeated pregnancies and naloxone.

Aging of the female reproductive system may be regulated by changes at the hypothalamic, pituitary, and ovarian levels. Long-term ovariectomy (LT-OVX) and/or multiple pregnancies delay age-related deterioration of several parameters of reproductive potential in rodents. We tested whether long-term suppression of cyclic ovarian hormone release that is normally associated with the 4- to 5-day estrous cycle decelerates age-related decreases in the frequency of luteinizing hormone (LH) pulses to assess whether hormonal milieu influences the rate of aging of the pulse generator. We determined the percentage of rats exhibiting pulsatile LH secretion, mean LH levels, and amplitude and frequency of LH pulses in seven groups of ovariectomized (OVX) rats. Young (3-4 mo), middle-aged (8-10 mo), and old (18-22 mo) virgin rats, ovariectomized 4 wk (4WK-OVX) prior to experimentation, were used to determine the effect of age. The effect of long-term ovarian hormone deprivation was tested by ovariectomizing rats at 2-3 mo of age and using them when they were middle-aged (8-10 months) or old (18-22 mo). The effect of deprivation of cyclic increases in ovarian hormones associated with repeated estrous cycles was tested by using retired breeder (RB) rats that had been ovariectomized 4 wk prior to experimentation. Each rat was implanted with a right atrial cannula and bled the next day at 10-min intervals for 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

[Comparative studies of prolactin, estrogen, progesterone and androgen receptor levels in human breast cancers].

A receptor for lactogenic hormones (prolactin of several species and human growth hormone) was characterized in crude plasma membrane preparations of adult female rat liver. The binding of 125J-labeled prolactin to receptors was specific, saturable, reversible, and of high affinity (Kd = 0.23 x 10(-10)M). The maximum amount of prolactin specifically bound to liver of untreated female rats was 45 fmol/mg protein, whereas no specific prolactin binding was detected in plasma membrane preparations of adult male or immature rats. With this assay, a specific and reversible binding of ovine prolactin was detected in plasma membrane preparations of 25 human breast cancers, ranging from 2-29% of total activity. The estrogen-, progesterone- and androgen receptor content was determined in the breast cancer specimens using the dextran-coated charcoal method. Specimens with the highest specific prolactin binding showed the lowest steroid receptor concentrations, but no significant correlation between estrogen-, progesterone-, androgen-, and prolactin receptor content and other prognostic factors was observed in our series. We conclude, that steroid and prolactin receptors are expressed independently in human breast cancer.

Adult↗
PubMed1988

[Pathophysiology of hyperprolactinemia in breast cancer].

To characterize the prolactin secretion in human breast cancer, plasma prolactin levels were measured in 514 patients with breast cancer in long term follow-up studies. In hyperprolactinemic patients suppression and stimulation tests were performed and the 24-h secretion profile was recorded. Tissue extracts and sera of hyperprolactinemic breast cancer patients were incubated with cultured pituitary cells in vitro to detect a prolactin releasing activity in these specimens. 44% of breast cancer patients developed hyperprolactinemia in the course of the disease. In 35% of measurements hyperprolactinemia was induced by non tumor related causes, e.g. prolactin-stimulating drugs, surgery, uremia, prolactinoma. Excluding such influences on the prolactin level, hyperprolactinemia over 1,000 mU/l was almost only found in patients with progressive metastatic disease. In these patients hyperprolactinemia was associated with tumor load, but not correlated to BSR, CEA or prognostic factors. Hyperprolactinemia in breast cancer was not of paraneoplastic origin. No prolactin-releasing activity was detected in tumor tissue and sera of hyperprolactinemic breast cancer patients.

Breast↗
PubMed1988

Inhibitory effect of oxytocin and vasopressin on steroid release by cultured porcine luteal cells.

Previously, we have demonstrated the presence of substances reacting like arginine vasopressin (AVP) and oxytocin (OXT) in acid extracts of corpora lutea (CL) of pigs by RIA. The present study examined purified extracts of CL by using HPLC. The results of these experiments show that CL of nonpregnant sows contain AVP and OXT. Little is known about possible auto- and paracrine effects of AVP and OXT in the ovary. Therefore, we investigated the influence of AVP and OXT on progesterone, estradiol, and androstenedione secretion in porcine luteal cell cultures from nonpregnant sows. Progesterone and androstenedione secretion increased significantly (P less than 0.05) in the presence of ovine LH (oLH), whereas no change in basal estradiol levels could be observed under the same conditions. When AVP or OXT was added to the culture system a dose-dependent inhibition of basal as well as oLH-stimulated progesterone secretion was measured. Under basal conditions, a dose of 1 pg AVP/ml decreased progesterone secretion significantly (P less than 0.05), but to reach the same effect in the presence of OXT a dose of 100 ng/ml was necessary. In the presence of oLH the addition of as little as 0.01 pg AVP/ml inhibited progesterone secretion significantly (P less than 0.05). On the other hand, 10 ng OXT/ml or higher doses were needed to decrease oLH-stimulated progesterone release. In the presence of specific peptide antagonists the inhibitory effect on progesterone release was abolished. These results suggest that AVP and OXT effects are mediated through specific receptors. OXT and AVP also inhibited androstenedione secretion, but had no effect on estradiol secretion. Calculation of the ED50 data from dose-response curves of both peptides show that AVP is about 10(4)-fold more active than OXT in inhibiting in vitro progesterone and androstenedione secretion. This suggests that AVP as well as OXT may play an important role in the regulation of ovarian function.

Androstenedione↗
PubMed1988

Differential response of substance P-containing subtypes of adrenomedullary cells to different stressors.

Adrenal medullary cells produce not only the catecholamines norepinephrine and epinephrine but also a number of peptides; hence, they can be subclassified according to their peptide quality. The present study was an attempt to test whether different stressors address different subclasses of adrenal medullary cells. The adrenal gland of intact male rats was implanted with a dialysis system, and the jugular vein was catheterized. One day after surgery, the adrenal dialysis system was connected to a perfusion pump, and Ringer solution was used for dialysis; dialysate fractions were collected at 15-min intervals, and blood was withdrawn at the end of each fraction period after a 2-h equilibration period. The basal release rates of pituitary PRL and adrenal corticosterone, measured in plasma, and of epinephrine, norepinephrine, and substance P (SP) measured in the adrenal dialysates, were constant during the preshock period. SP concentrations in the blood were below the detection limit of the RIA. Application of mild electric foot shock stress resulted in a marked increase in adrenal catecholamine and SP release. Plasma PRL and corticosterone levels also rose during the time of exposure to foot shock, but plasma SP concentrations remained at undetectable values. In contrast, a metabolic stress i.e. insulin-induced hypoglycemia, did not affect adrenal SP release, although adrenal catecholamine release increased to a larger degree than after foot shock stress. Plasma PRL and corticosterone levels also increased during insulin-induced hypoglycemia. It is concluded that an exogenous stressor (electric foot shock) activates adrenomedullary cells containing catecholamines and SP, whereas these cells are not activated by the stress of insulin-induced hypoglycemia.

Adrenal Medulla↗
PubMed1988

Pituitary-dependent effects of estradiol-17-beta on catecholamine turnover rates, gamma-aminobutyric acid and glutamate concentrations in various hypothalamic and limbic brain structures.

Estrogens exert many effects in a variety of hypothalamic and mesolimbic structures. Whether the actions of the estrogens are direct or indirect, possibly involving anterior pituitary hormones, is largely unknown. We therefore studied catecholamine turnover rates, gamma-aminobutyric acid and glutamate concentrations in various hypothalamic and mesolimbic structures in estrogen-treated hypophysectomized (hypox) rats and compared the measured parameters with those in sham hypophysectomized (sham) animals. Results clearly demonstrate that many of the effects of estrogen require an intact pituitary. Dopamine turnover rates in hypox rats were significantly reduced in the hypothalamus and the striatum, whereas they increased in the medial septum and medial preoptic area in comparison with sham rats. Norepinephrine turnover rates were reduced in the anterior mediobasal hypothalamus, somatosensory cortex and the nucleus accumbens of hypox animals in comparison with the sham-operated animals. In contrast, norepinephrine turnover was accelerated in the mediocortical amygdala and posterior medial basal hypothalamus of hypox rats. A significant reduction of epinephrine turnover was evident in the nucleus accumbens of hypox rats. Gamma-aminobutyric acid concentrations increased in the medial septum, anterior and posterior part of the mediobasal hypothalamus, but decreased in the mediocortical amygdala of hypox animals. Concentrations of glutamate were also decreased in the mediocortical amygdala in hypox animals. These results indicate that many direct effects of estrogens in the brain are accompanied by indirect effects which require an intact pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Further evidence that preoptic anterior hypothalamic GABAergic neurons are part of the GnRH pulse and surge generator.

The in vivo release rates of GABA from the preoptic/anterior hypothalamic area (PO/AH) of ovariectomized rats were assessed by means of a focal perfusion cannula system. Seven days after surgery all animals received a sc silastic capsule implant containing either estradiol-17 beta (E2) or corn oil, and they were perfused 3 days later. Perfusate fractions were sampled at 5-min intervals and blood was collected every 10 min over a period of 5 h. In ovariectomized animals PO/AH GABA release was pulsatile without any diurnal rhythm. Prior to frequency analysis by means of the pulsar-programme, LH and GABA values were z-transformed. Significant LH peaks of all examined ovariectomized rats were superimposed and GABA data were arranged accordingly. It became evident that LH episodes are preceded by a significant reduction of preoptic anterior hypothalamic GABA release. The secretion patterns of GABA and LH were profoundly affected by E2 replacement. During early noon when LH levels were low, constantly elevated hypothalamic GABA release rates were observed in E2-substituted rats in comparison to ovariectomized rats. GABA release rates fell significantly during the E2-induced LH surge. Our previous demonstration of the existence of a large number of estrogen-respective GABAergic neurons in the PO/AH is suggestive of these neurons changing their activity in response to estrogen treatment. We conclude that these estrogen-respective GABAergic neurons are involved in the generation of GnRH pulses as well as in the generation of the so-called positive feedback effect of E2 on LH release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Angiotensin II/III and substance P in human follicular fluid obtained during IVF: relation of the peptide content with follicular size.

Ovarian follicular fluid (FF) of a number of species contain regulatory peptides secreted by granulosa cells or by autonomic nerve terminals. In this report we demonstrate the presence of authentic (HPLC-verification) angiotensin II and III as well as of substance P (SP) in human FF obtained from hMG stimulated infertile patients undergoing in vitro fertilization. Angiotensin II/III (AII/III), estradiol (E2) and progesterone concentrations increase with the size of the follicles. SP concentrations did not vary significantly in FF of various sizes. These peptide concentrations in FF are about 10-fold higher than those measured in the serum of the same patients. Attempts to correlate SP, AII/III, E2 and progesterone concentrations in the individual FF with the ability of an oocyte to be fertilized, failed. Neither AII/III, SP, E2 nor progesterone concentrations were different in these subclasses of FF. Follicles of patients punctured under general anesthesia contained significantly more SP than follicles of patients which had lumbar analgesia. AII/III concentrations were the same in FF of both treatment groups. The presence of angiotensin II and III in FF in increasing concentrations depending on the maturity of the follicle and the inability of general anesthesia to affect the AII/III concentrations suggests that this peptide is produced within the ovary.

Anesthesia, General↗
PubMed1988

[Relation of the inhibition of cortisol synthesis in vivo to plasma etomidate concentrations].

Young, healthy male patients undergoing body surface surgery under fentanyl-nitrous oxide-oxygen anesthesia were given an etomidate bolus for induction (0.3 mg/kg body weight) followed by a continuous infusion (0.36 mg.kg-1.h-1). The total etomidate dose was 63 +/- 6.4 mg (mean +/- standard error). Basal cortisol levels as well as the adrenocortical response to exogenous synthetic ACTH1-24 (0.25 mg i.m.) were determined preoperatively, at the end of anesthesia, and 6 and 20 h postoperatively. The reduction of the response to ACTH stimulation measured postoperatively as compared to preoperatively was calculated as percentage of the preoperative response. Plasma concentrations of etomidate were measured at the same sample times by gas chromatography. At the end of anesthesia the plasma level was 570 +/- 131 nM (mean +/- standard error). It decreased to 99 +/- 23 nM 6 h later and to 43 +/- 3 nM 20 h postoperatively. The plasma concentrations were plotted against the inhibition data. We found a sigmoid relationship between the relative inhibition and the log of the etomidate concentrations. We determined an EC50 for inhibition of 110 nM that agrees well with published data. We also found that the cortisol response was not completely suppressed at the concentrations measured here. This supports the results of a previous study in which we found that patients undergoing cardiovascular surgery still exhibited intra- and postoperative cortisol increases although they had been given large doses of etomidate. We conclude that the suppression of corticosteroid synthesis caused by etomidate is concentration-dependent. The suppression is negligible at concentrations lower than 40 nM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗