Hemodynamic actions of corticotropin-releasing hormone and proopiomelanocortin derivatives in septic patients.

Proopiomelanocortin (POMC) derivatives and mRNA of POMC have been detected in cardiomyocytes and vascular smooth muscle cells. Increased plasma levels of POMC derivatives have been found in septic patients during cardiovascular deregulation; therefore, we evaluated whether corticotroph-type (ACTH, ß-endorphin, ß-lipotropin) or melanotroph-type (α-melanocyte-stimulating hormone and N-acetyl-ß-END) POMC derivatives have influences on patients' hemodynamics during sepsis. Seventeen septic patients were monitored by pulmonary artery catheter and corticotropin-releasing hormone (CRH) tests were performed by intravenous administration of 100 µg CRH. Before, 15, 30, 45, and 60 minutes after CRH administration, hemodynamic variables were measured, and plasma concentrations of POMC derivatives were determined. After CRH administration, heart rate, cardiac index, and stroke index increased, and the systemic vascular resistance index decreased; moreover, a correlation between ACTH concentration and stroke index as well as an inverse correlation between (α-melanocyte-stimulating hormone concentration and systemic vascular resistance index was observed. CRH and ACTH may have opposite effects on the blood pressure (mean arterial pressure). Immediately after CRH injection mean arterial pressure decreased. ACTH (in contrast to ß-endorphin or ß-lipotropin), released into the cardiovascular compartment 15 minutes after CRH injection, might have raised mean arterial pressure as compatible with the correlation between ACTH levels and stroke index. (α-melanocyte-stimulating hormone appears to have a vasodilative effect during sepsis.

beta-Endorphin is not detectable in plasma from normal human subjects.

beta-Endorphin is not detectable in plasma from normal human subjects when measured under baseline conditions or after the subjects have received vasopressin, an agent that elevates beta-lipotropin and adrenocorticotropic hormone (ACTH). Significant amounts of beta-endorphin are present in plasma of patients with endocrine disorders associated with increased ACTH and beta-lipotropin production. Highly purified, natural beta-lipotropin is not peripherally converted to beta-endorphin in vivo in normal subjects.

Simultaneous assay of immunoreactive beta-lipotropin, gamma-lipotropin, and beta-endorphin in plasma of normal human subjects, patients with ACTH/lipotropin hypersecretory syndromes, and patients undergoing chronic hemodialysis.

We have studied the relative concentrations of the human immunoreactive (IR) peptides gamma-lipotropin (hgammaLPH, [1-58]hbetaLPH), beta-lipotropin (hbetaLPH), and beta-endorphin (hbetaEND, [61-91]hbetaLPH) using gel exclusion chromatography together with a specific radio-immunoassay (RIA) for hgammaLPH and a RIA that (because hbetaEND is the COOH-terminus of the hbetaLPH molecule) measures both hbetaEND and hbetaLPH on an equimolar basis. In normal subjects, basal plasma IR-hgammaLPH was often undetectable (<12.5 fmol/ml), but ranged up to 21 fmol/ml, and IR-hbetaEND/hbetaLPH was 10.8+/-0.7 fmol/ml; previous studies by others suggest that most of the IR-hbetaEND/hbetaLPH was probably hbetaLPH. Both IR-hgammaLPH and IR-hbetaEND/hbetaLPH were significantly elevated (P < 0.001) in patients undergoing chronic hemodialysis (101.5+/-12.7 and 23.8+/-2.0 fmol/ml, respectively). Their IR-hgammaLPH coeluted with standard hgammaLPH as a single peak, and IR-hbetaEND/hbetaLPH coeluted with hbetaLPH; no distinct peak of IR-hbetaEND was observed. In patients with ACTH/LPH hypersecretion due to Addison's disease, Nelson's syndrome, or ectopic ACTH syndrome, IR-hgammaLPH and IR-hbetaEND/hbetaLPH were both elevated, and IR-hbetaEND/hbetaLPH eluted as two peaks, one coeluting with hbetaLPH and the other with hbetaEND. The molar concentrations of all three peptides were significantly correlated with one another. The lower concentrations of endogenous IR-hbetaEND observed may be due in part to its apparent shorter plasma half-life, as estimated in an Addison's patient given a cortisol infusion. The biologic significance of these three peptides in circulating blood is still unknown. The increased levels of hbetaLPH and hgammaLPH in plasma of patients with chronic renal failure suggest that the kidney may be an important organ for their metabolism.

Presence of immunoreactive beta-endorphin in normal human plasma: a concomitant release of beta-endorphin with adrenocorticotropin after metyrapone administration.

To elucidate whether or not beta-endorphin exists in plasma of normal subjects, plasma extracts obtained before and after metyrapone administration were subjected to gel exclusion chromatography, and fractions obtained were assayed by a sensitive radioimmunoassay for beta-endorphin. The basal plasma level of beta-endorphin was 5.8 +/- 1.1 pg/ml (mean +/- SE, n = 5), which rose significantly to the level of 48.9 +/- 3.8 pg/ml after a single oral dose (30 mg/kg of body wt) of metyrapone administration (P less than 0.001). Plasma ACTH levels also increased from the mean basal level of 73 +/- 4 pg/ml to 269 +/- 41 pg/ml after metyrapone administration. These results indicate that beta-endorphin, distinct from beta-lipotropin, exists in normal human plasma and that it is released from the pituitary concomitantly with ACTH.

The nature of the immunoreactive lipotropins in human plasma and tissue extracts.

This study was designed to establish definitively the nature of immunoreactive lipotropin (IR-LPH) in human plasma and tissue extracts. Using gel filtration, gel filtration under denaturing conditions, cationic exchange chromatography, immunoprecipitation, and radioimmunoassay, we have studied normal and tumorous human pituitaries, ectopic ACTH- and LPH-secreting tumors, plasma from normal subjects before and after dexamethasone administration, and plasma from patients with primary adrenal insufficiency and pituitary and nonpituitary ACTH- and LPH-secreting tumors. Except in the plasma and tumors of occasional patients with ectopic ACTH syndrome, the smallest IR-LPH appears to be lambda-lipotropin (lambdaLPH), which is often the predominant and occasionally the only IR-LPH present. The other major peptide appears to be betaLPH, a 91-amino acid molecule that contains lambdaLPH as its 1-58 sequence. Larger immunoreactive materials were observed in some specimens, but the "big" LPH in one plasma was shown to be lambdaLPH bound to IgG.The weak melanocyte-stimulating activity of LPH suggests that ACTH may be the principal pigmentary hormone in man. The fact that lambdaLPH, rather than betaLPH, is the predominant form in plasma suggests that the enkephalin-endorphin opiate peptides, which are contained in the "missing" 59-91 sequence from the betaLPH precursor of lambdaLPH, may be secreted in parallel with ACTH under both physiological and pathological conditions in man.

Plasma levels of corticotroph-type pro-opiomelanocortin derivatives such as beta-lipotropin, beta-endorphin(1-31), or adrenocorticotropic hormone are correlated with severity of postoperative pain.

BACKGROUND: In the pituitary of lower species, pro-opiomelanocortin is expressed in corticotroph cells of the anterior and in melanotroph cells of the neurointermediate lobe; enzymatic processing in the corticotrophs results in the release of adrenocorticotropic hormone, beta-lipotropin, or beta-endorphin. In the melanotrophs, these fragments are further modified, eg, by N-terminal acetylation. In the human pituitary, these enzyme systems are located within the same cells in the anterior lobe. We studied the reactions of the pro-opiomelanocortin system under preoperative conditions as well as under postoperative pain. METHODS: In 17 patients undergoing hip or knee arthroplasty, we determined plasma concentrations of N-acetyl-beta-endorphin immunoreactive material, authentic beta-endorphin [beta-endorphin(1-31)], adrenocorticotropic hormone, beta-lipotropin immunoreactive material, and cortisol, as well as pain severity rated by the patients using a visual analogue scale before surgery, after surgery but still under spinal anesthesia, under postoperative pain, and 1 day after surgery. RESULTS: Only low levels of N-acetyl-beta-endorphin immunoreactive material were measured in 16 out of 17 patients. High concentrations (1st quartile/median/3rd quartile; pmol/L) of adrenocorticotropic hormone (22.5/55.8/124) and beta-lipotropin immunoreactive material (6.6/34.6/142) were observed under postoperative pain, accompanied by a small increase of beta-endorphin(1-31) concentrations (0.0/6.1/10.9). Preoperatively small but significantly elevated levels of corticotroph-type and melanotroph-type pro-opiomelanocortin derivatives were observed; in contrast, spinal anesthesia suppressed all pro-opiomelanocortin fragment release. Postoperative pain severity correlated with postoperative adrenocorticotropic hormone, beta-lipotropin immunoreactive material, and beta-endorphin(1-31) concentrations. CONCLUSIONS: We conclude that the melanotroph-type pro-opiomelanocortin system is not activated under postoperative pain; the increase of corticotroph-type pro-opiomelanocortin fragment levels is different in quantity and proportion under preoperative conditions or postoperative pain, respectively.

Multiple markers for lung cancer diagnosis: validation of models for advanced lung cancer.

Sera from 171 patients with advanced lung cancer, from 110 normals, and from 123 subjects with benign respiratory diseases were analyzed for 10 substances to detect lung cancer: ferritin, lipid-bound sialic acid, total sialic acid, beta 2-microglobulin, lipotropin, the alpha and beta subunits of human chorionic gonadotropin, calcitonin (two assays), parathyroid hormone, and carcinoembryonic antigen. Individual markers were studied, and optimal combinations of markers were sought for discriminating lung cancer patients from normals and from patients with benign lung disease. Numerous methods for combining the markers were examined, but the methods of logistic regression and recursive partitioning were finally adopted. The best discrimination rules we could find used only carcinoembryonic antigen (CEA) and total sialic acid (TSA). The performance of these rules was validated on an independent serum panel containing sera from 68 patients with advanced lung cancer, from 40 normals, and from 52 patients with benign respiratory disease. The combination rules based on TSA and CEA performed better than a rule based on CEA alone. Logistic discrimination rules with TSA and CEA that were designed to have 95% specificity achieved 54% sensitivity for discriminating advanced lung cancer from normal controls and 52% sensitivity for discriminating advanced lung cancer from controls with benign disease. Some aspects of clinical applicability are discussed, including planned studies for localized lung cancer and the requirement for further testing in specific clinical settings.

Increased evening activation of the hypothalamic-pituitary-adrenal axis in depressed patients.

OBJECTIVE: To determine whether depressed patients demonstrate hypothalamic-pituitary-adrenal (HPA) axis activation during the late afternoon and evening, a time when the HPA axis is usually quiescent in normal subjects. METHODS: We administered metyrapone, an 11-beta-hydroxylase inhibitor of cortisol synthesis, to normal controls and depressed patients between 4 and 10 PM. Metyrapone blockade of cortisol secretion would amplify any HPA axis secretion. RESULTS: In 10 normal control subjects, administration of metyrapone lowered plasma cortisol levels to a mean of 36 nmol/L. No rebound corticotropin or beta-endorphin secretion was seen in these normal controls between 4 and 10 PM, supporting the existence of a period of minimal endogenous corticotropin releasing factor drive. Compared with a group of placebo-treated depressed patients (n = 10), metyrapone-treated depressed subjects (n = 17) had significantly decreased plasma cortisol concentrations. However, in contrast to normal controls treated with metyrapone, metyrapone-treated depressed patients demonstrated rebound corticotroph secretion, particularly between 7:30 and 10 PM (P = .036 for patients vs normal controls for beta-endorphin secretion from 4:30 to 10 PM). CONCLUSION: These data support the hypothesis of increased corticotropin releasing factor drive in the evening in depressed subjects and are in agreement with the longstanding observation of "early escape" from dexamethasone suppression between 4 and 11 PM in depressed patients.

Loss of glucocorticoid fast feedback in depression.

A rate-sensitive fast-feedback inhibition of stress-induced corticotropin secretion by glucocorticoids is well documented in rats. Studies in patients with Cushing's disease or adrenal insufficiency have also supported the existence of fast feedback in humans. However, few studies exist in normal healthy subjects or depressed patients. This study compared fast-feedback inhibition of beta-endorphin/beta-lipotropin secretion by hydrocortisone in 16 control subjects and 16 depressed patients. A fast-feedback effect of hydrocortisone on beta-endorphin/beta-lipotropin secretion during the hour of the hydrocortisone infusion was demonstrated in control subjects. Depressed patients demonstrated no increase in beta-endorphin/beta-lipotropin concentrations during the infusion. These data suggest a decreased sensitivity to glucocorticoid fast feedback in depressed patients and complement existing studies demonstrating decreased sensitivity to proportional feedback by dexamethasone in depressed patients. We believe the data presented herein are the first demonstration that abnormal feedback occurs at the level of the brain rather than pituitary in depressed patients.

Differential plasma beta-endorphin, beta-lipotropin, and adrenocorticotropin responses to stress in rats.

This study was designed to compare the amounts of ACTH, beta-endorphin (beta END), and beta-lipotropin (beta LPH) that are present in plasma under basal conditions and after single and repeated administration of a discrete 2-min restraint stress both in intact and in chronically adrenalectomized rats. In intact rats, application of a 2-min restraint stress produced rapid parallel increases in plasma concentrations of radioimmunoassayable ACTH and beta END/beta LPH (the total of beta END-like immunoreactivities), with peaks 2.5-5 min after onset of the stress and return almost to basal concentrations by 30 min. Gel exclusion chromatography [Sephadex G-50 (fine)] and subsequent RIA revealed that plasma obtained from control nonstressed intact rats contained much greater quantities of beta END (94% of the total beta END/beta LPH immunoreactivity) than beta LPH. In contrast, equal amounts of beta END and beta LPH were present in plasma of intact rats 2.5-10 min after onset of the 2-min restraint stress. Chronically adrenalectomized rats lacking glucocorticoid-negative feedback had significantly higher basal plasma concentrations of beta END/beta LPH and ACTH than those present in intact rats. Furthermore, the plasma responses of both beta END/beta LPH and ACTH to stress were markedly enhanced in chronically adrenalectomized rats compared to the corresponding responses in intact rats. Gel exclusion chromatography revealed that both the higher basal concentration and the enhanced plasma beta END/beta LPH response to stress in adrenalectomized rats resulted primarily from increases in the beta LPH component, with lesser increases in the beta END component. In contrast to the proportion in intact rats, in chronically adrenalectomized rats, beta END represented about 27% of the total beta END/beta LPH immunoreactivity in the basal state and about 18% 5-10 min after the onset of restraint stress. In intact rats, the plasma ACTH responses to a subsequent stress applied 5 min (a time when peak plasma levels of hormones are present) or 30 min (a time when the plasma hormone concentrations have returned to prestress levels) after the initial stress and the plasma beta END/beta LPH response to a second stress applied at 30 min were equal to the corresponding hormone responses to a single stress. In contrast, the plasma beta END/beta LPH response to the subsequent stress applied 5 min after the initial stress was significantly potentiated in intact rats.(ABSTRACT TRUNCATED AT 400 WORDS)

The hormonal actions of corticotropin-releasing factor in sheep: effect of intravenous and intracerebroventricular injection.

The 41-residue ovine corticotropin releasing factor (CRF) was administered iv and intracerebroventricularly (icv) to merino sheep. A significant rise in plasma ACTH, beta-lipotropin (beta LPH) and cortisol was demonstrated after the administration of 200 micrograms, iv. A highly significant correlation between the increments in plasma ACTH and beta LPH was observed. The plasma ACTH rise was evident within 5 min and was abolished by the prior administration of 0.4-4.0 mg dexamethasone. No significant rise in plasma GH, LH, PRL, insulin, glucagon, pancreatic polypeptide, met-enkephalin, angiotensin II, aldosterone, or vasopressin could be demonstrated. Although smaller doses of CRF (50 ng to 5 micrograms) were effective when given icv, the ACTH response was more delayed. It is concluded that CRF stimulates a rapid increase in the secretion of ACTH and beta LPH in sheep. Suppression of this response by dexamethasone indicates that glucocorticoids are capable of acting on the pituitary to inhibit the ACTH response to CRF. The delayed response when CRF is given icv may be due to diffusion. The action of CRF appears to be relatively specific, in that the plasma concentrations of the other pancreatic, pituitary, and adrenal hormones measured were not affected.

Plasma immunoreactive proopiomelanocortin peptides and cortisol in normal dogs and dogs with Addison's disease and Cushing's syndrome: basal concentrations.

We measured basal plasma concentrations of the immunoreactive (IR) proopiomelanocortin (POMC)-derived peptides ACTH, beta-lipotropin (beta LPH), beta-endorphin (beta END), and alpha MSH in 160 normal dogs, 32 dogs with Addison's disease, 42 dogs with adrenocortical tumors causing Cushing's syndrome, and 169 dogs with pituitary-dependent Cushing's disease. In normal dogs, plasma IR-POMC peptide levels were similar to those in man, except that IR-alpha MSH, a pars intermedia POMC product, was readily detected. In Addisonian dogs, plasma cortisol was decreased, and the IR-POMC peptides were increased, except for IR-alpha MSH, which was normal. In 7 Addisonian dogs given dexamethasone, elevated plasma IR-ACTH, beta LPH, and beta END levels fell dramatically. In dogs with Cushing's syndrome due to adrenal tumors, plasma IR-ACTH, beta LPH, and beta END were decreased, and cortisol was increased, but IR-alpha MSH was normal. Dogs with Cushing's disease due to pars distalis tumors had elevated plasma IR-ACTH, beta LPH, beta END, and cortisol, but normal IR-alpha MSH; their plasma cortisol was suppressed by dexamethasone. There appeared to be 2 types of pars intermedia tumors causing Cushing's disease: 1 dexamethasone nonsuppressible and with disproportionately high plasma IR-alpha MSH levels, the other relatively dexamethasone suppressible and with normal to slightly elevated IR-alpha MSH levels. These 2 pars intermedia tumor types may arise from 2 distinct normal canine pars intermedia cell types. Canine Cushing's disease may provide a useful model for variants of the disorder in man.

Morphine and naloxone: effects on beta-endorphin immunoreactivity in canine plasma and secretions from rat pituitaries.

Morphine and naloxone were administered to five dogs to assess their effects on endogenous opioid release. Morphine (3 mg/20 kg) produced a significant (P less than 0.05) increase in plasma beta-endorphin immunoreactivity(beta EI) compared to saline control. The peak stimulation [19.2 +/- 4.97 baseline to 48.1 +/- 6.82 (SEM) pg/ml] occurred at +10 min and rapidly returned to preinjection levels at +60. At a dose 10 times equipotent to circulating basal beta EI, morphine (4-6 micrograms) failed to affect beta EI release. Naloxone, surprisingly, also caused a significant (P less than 0.025) release of beta EI. After naloxone, beta EI rose from a preinjection baseline of 36.4 +/- 5.82 pg/ml to a peak of 172 +/- 44.1 pg/ml at 45 min post injection. Naloxone pretreatment also obscured the effect of subsequently injected morphine (3 mg/20 kg). In three naloxone-treated dogs, gel chromatography of pooled basal and peak plasma revealed a preponderance of beta-lipotropin compared to beta-endorphin. To determine the site of stimulation of beta EI by opiates and opioids, a series of rat anterior pituitary incubations were performed. Neither morphine (10(-6) M) nor D-Ala2-methionine enkephalinamide (10(-6) M) nor naloxone (10(-6) M) had an effect significantly different from control medium on the release of beta EI from the pituitaries. In a second set of experiments we compared the effect on beta EI release of hypothalamic median eminence extract alone or with morphine. Hypothalamic median eminence extract at two concentrations produced significant release of beta EI, which was unaffected by the addition of morphine. These results suggest that stimulation of release of endogenous opioid peptides by opiates occurs at a suprapituitary level.

A specific radioimmunoassay for human beta-lipotropin.

A homologous RIA for human beta-lipotropin (beta hLPH) has been developed. At a final dilution of 1:24,000, the antiserum employed shows cross-reaction with beta hLPH but none with human beta-MSH (beta hMSH), and it is concluded that the antigenic determinant lies within the N-terminal 1-36 region of beta hLPH. With extraction of 3-ml plasma samples, the assay is sufficiently sensitive to measure circulating beta hLPH levels in normal individuals at 0900 h (25-200 pg/ml). There is a circadian variation with levels falling to (less than 20-80 pg/ml) at 2300 h. beta hLPH levels rise after metyrapone and after insulin-induced hypoglycemia, and fall after administration of dexamethasone. In patients with a variety of diseases of the pituitary-adrenal axis, levels of beta hLPH follow immunoreactive ACTH levels, although the two are not always secreted on a 1:1 molar basis.

Beta-lipotropin and cortisol responses to an intravenous infusion dexamethasone suppression test in Cushing's syndrome and obesity.

An i.v. infusion dexamethasone (Dex) test was used to investigate the ACTH feedback response in 9 normal subjects, 12 obese patients, and 11 patients with Cushing's syndrome. Dex phosphate was infused iv for 4 h, starting at 1100 h (1 mg/h). Plasma concentrations of beta-lipotropin (beta LPH) and cortisol were measured every 20 min between 0900 and 1600 h, then every 2 h until midnight and at 0900 h the next day. In normal subjects and obese patients, plasma beta LPH and cortisol concentrations fell rapidly to less than 40 ng/liter and 3 micrograms/dl, respectively, at the end of Dex infusion. Subsequent values remained low through 0900 h the next day. In 7 patients with Cushing's disease, basal plasma beta LPH and cortisol concentrations declined by greater than 50% during the Dex infusion. In these patients, rapid escape from suppression occurred between 1600 and 2400 h; by 0900 h the following day, beta LPH and cortisol levels were higher than 100 ng/liter and 10 micrograms/dl, respectively. In 3 patients with adrenal tumors, beta LPH concentrations were low, and cortisol concentrations did not decline during the Dex infusion. In 1 patient with ectopic ACTH secretion, beta LPH concentrations were high and were not suppressed by the Dex infusion. We conclude that the iv infusion Dex suppression test can distinguish patients with Cushing's syndrome from normal or obese subjects and can aid in the etiological diagnosis of Cushing's syndrome.

Substantial rise of plasma beta-endorphin levels after insulin-induced hypoglycemia in human subjects.

To elucidate whether insulin-induced hypoglycemia enhances the release of beta-endorphin in man, plasma extracts obtained from healthy subjects and patients with Graves' disease before and 45 min after insulin injection were subjected to gel chromatography, and the fractions obtained were measured by RIA for beta-endorphin. In four healthy subjects, basal plasma beta-endorphin levels were less than 3 to 3.1 pg/ml, and the levels rose substantially to 47.5 +/- 12.4 pg/ml (mean +/- SE) 45 min after insulin injection. Basal plasma beta-endorphin levels in three hyperthyroid patinets (less than 3 to 3.8 pg/ml) did not seem to be different from those in healthy subjects; however, the rise after insulin injection tended to be higher in cases of hyperthyroidism, with a peak value of 68.5 +/- 9.7 pg/ml. Plasma beta-lipotropin and ACTH levels also rose in parallel with beta-endorphin in response to insulin-induced hypoglycemia in both healthy subjects and hyperthyroid patients. It would thus appear that beta-endorphin, like ACTH or beta-lipotropin, is released in human subjects by hypoglycemic stress.

Plasma beta-endorphin and beta-lipotropin in the human fetus at delivery: correlation with arterial pH and pO2.

Beta-endorphin-like immunoactivity was measured in the umbilical cord plasma of 45 term human fetuses. Mean concentration was 91 +/- 16 (SEM) pg/ml,an the normal adult level of 30.7 +/- 2.7 pg/ml. This immunoactivity was further characterized in 10 cases by Sephadex G-50 chromatography to separate beta-endorphin from beta-lipotropin (beta-LPH). Mean beta-endorphin and beta-LPH concentrations were 57 +/- 12.8 and 455 +/- 101 pg/ml, respectively. Both were higher (P less than 0.01) than the mean beta-endorphin and beta-LPH concentrations reported in the adult. The mean molar beta-endorphin to beta-LPH ratio was 0.35 in the fetus and 0.36 in the adult. In 17 fetuses whose umbilical arterial and venous concentrations were measured separately, mean beta-endorphin-like immunoactivity was higher in the artery than in the vein. A highly significant negative correlation (r = -0.831; P less than 0.001) was present between umbilical arteiral pH and beta-endorphin-like immunoactivity. A negative correlation (r = -0.611; P less than 0.005) with arterial pO2 was also noted. We conclude that high levels of beta-endorphin-like immunoactivity, composed of both beta-endorphin and beta-LPH, circulate in the human fetus at term, and that hypoxia and secondary acidosis may be major stimuli to the release of these peptides.

beta-Endorphin and beta-lipotropin plasma levels in hirsute women: correlation with body weight.

Based on the findings of elevated circulating beta-endorphin (beta-END) levels in genetically obese (fa/fa) fats and the reversal of the overeating of genetically obese (ob/ob) mice by naloxone, circulating beta-END and beta-lipotropin (beta-LPH) levels were measured in 8 hirsute, hyperandrogenic, oligo-amenorrheic women of varying weights. Circulating beta-END and beta-LPH levels were significantly elevated (p less than .001) above the levels in nonobese control subjects and were positively correlated with body weight (p less than .025). Based on these data and indirect evidence in the literature, we propose a role may exist for beta-END and/or beta-LPH in human obesity and in adrenal androgen secretion.

Simultaneous determination of human plasma immunoreactive beta-lipotropin, gamma-lipotropin, and beta-endorphin using immuno-affinity chromatography.

Since plasma ACTH, beta-lipotropin [beta-LPH-(1-91)], gamma-lipotropin (gamma-LPH: [beta-LPD-(1-58)]), and beta-endorphin (beta-EP: [beta-LPH-(61-91)]) are all derived from a common precursor molecule, their quantification in the same plasma under basal and stimulatory conditions should help to elucidate factors involved in their secretion and regulation. A sequential immune affinity chromatographic procedure was used to separate immunoreactive beta-LPH, gamma-LPH, and beta-EP on individual patient samples. Basal morning plasma concentrations [femtomoles per ml (to convert values to picograms per ml, femtomoles per ml values are multiplied by 10 for beta-LPH, by 5.8 for beta-LPH, by 4.5 for ACTH, and by 3.4 for beta-EP; n = 19; mean +/- SEM)] were: beta-LPH, 6.1 +/- 0.8; gamma-LPH, 4.4 +/- 0.5; and ACTH, 11.1 +/- 1.3. beta-EP was undetectable (< 1.5 fmol ml-1) in 7 of the 19 basal samples. The mean +/- SEM for the 12 remaining samples was 2.3 +/- 0.2. Insulin-induced hypoglycemia and Pitressin administration were associated with nearly equivalent increments of immunoreactive ACTH and beta-LPH concentrations. The resolving power of the technique was tested by separately applying the immunoreactive beta-LPH, gamma-LPH, and beta-EP fractions obtained from plasma pools to Sephadex G-50 gel filtration for molecular weight estimation. Greater than 88% of all immunoreactive material eluted with a Kav similar to the appropriate standard peptide markers. This immune affinity chromatographic system, therefore, permits simultaneous quantification of these peptides on small plasma volumes more rapidly and with greater resolution than when molecular sieve chromatography is used as an adjunct to RIA.