Yvonne Vrindts-Gevaert

PROLACTIN LEVELS DURING THE MENSTRUAL CYCLE

The levels of prolactin, FSH, LH, oestradiol and progesterone were measured daily during fourteen ovulatory cycles. The behaviour of FSH, LH, oestradiol and progesterone was classical. Non‐systematic changes occurred in prolactin levels during the course of the menstrual cycle with the highest level being either during the ovulatory period or during the luteal phase. However, the mean level of prolactin was significantly higher during the ovulatory and luteal phases than during the follicular phase. A direct relationship between oestradiol and prolactin levels was noted, although there was no correlation between prolactin on the one hand and FSH, LH and progesterone on the other.

Effects of dexamethasone on the profile of cytokine secretion in human whole blood cell cultures

EXPERIMENTAL OBJECTIVES The interaction between the endocrine and immune systems is a very intriguing area. Endogenous glucocorticoids, as end-effectors of the hypothalamo-pituitary-adrenal axis, inhibit the immune and inflammatory responses and are used as immunosuppressive drugs in many inflammatory, autoimmune and allergic diseases. The aims of this study were to investigate the effects of dexamethasone on the profile of cytokine secretion in whole blood cell cultures from healthy subjects and to analyse the gender-related sensitivity to dexamethasone on each cytokine secretion. RESULTS There was a significant inhibition by dexamethasone (from 1 to 100 nM) on the secretion of monokines (IL-1beta, IL-6, IL-8 and TNF alpha) and lymphokines (IL-2, IL-4, IL-10 and IFN gamma), either after LPS or PHA stimulation (P < 0.01). Interleukin 4 and IL-10 were less inhibited than IFN gamma (P < 0.05 at 1 nM, P < 0.01 at 10 nM and P < 0.001 from 100 nM to 10 microM). No gender difference was observed in the rate of inhibition of the secretion of each cytokine. CONCLUSION This study shows that the inhibition of cytokine secretion by dexamethasone is more marked on Th1-type cytokines than on Th2-type cytokines. These data support the idea that glucocorticoids may induce a shift from the Th1 to Th2 profile of cytokine secretion.

SERUM CONCENTRATIONS OF HUMAN CHORIONIC GONADOTROPHIN AND ITS ALPHA AND BETA SUBUNITS. 1. DURING NORMAL SINGLETON AND TWIN PREGNANCIES

Homologous radioimmunoassays have been developed for native hCG and its α and β subunits. Their specificities were assessed by analysis of the inhibition curves and by gel filtration of purified preparations of native hCG, hCGα and hCGβ, and of sera from pregnant women, on Sephadex G 100. Gel filtration data indicated a true cross‐reaction of native hCG in the hCGβ and hCGα assays of 0.5 and 0.35%, respectively. After validation of the RIA procedures for unfiltered serum assays, we have demonstrated that in 311 maternal sera obtained in 207 normal singleton pregnancies, free circulating hCGα increases continuously, whereas free hCGβ and native hCG peak between the 8th‐10th week. The ratio (hCGβ/hCG) x 100 is greatest during the first trimester (2–3%) and decreases thereafter to around 1%. The ratio (hCGα/hCG) x 100 is < 1% at the beginning of pregnancy, 2% at 14 weeks and 15–20% from the 23rd week onwards. The levels of hCG and its subunits are higher in fifty‐two samples obtained throughout normal twin pregnancies than in corresponding single pregnancies, but the ratios subunit: hCG are the same, suggesting qualitatively similar placental secretion in both types of pregnancy. Analysis of pregnancy sera by gel filtration and assay of hCG and subunits in eluant fractions confirmed that free α and β subunits are present in the circulation and that hCGα rises while hCG and hCGβ fall in late pregnancy. Heterogeneity of the circulating hCGβ subunit is also demonstrated.

Decreased corticosensitivity in quiescent Crohn's disease : An ex vivo study using whole blood cell cultures

Corticosensitivity influences the degree and theduration of an inflammatory reaction by altering targetcell responses to endogenous and/or exogenousglucocorticoids. Indeed, different clinical responses to glucocorticoids have been observed amongpatients with Crohns disease, suggesting differentdegrees of corticosensitivity in these subjects. Thepurpose of this study was to compare thecorticosensitivity of patients with quiescent Crohns disease tothat of healthy subjects (HS). Nineteen patients withquiescent Crohns disease and 14 HS were studied; allpatients were steroid-free for at least six months; 7 of the 19 were corticosteroid-dependent (CSD)and treated with nonglucocorticoid immunosuppressants atthe time of the study. Corticosensitivity was measuredby the inhibition of LPS-induced cytokine secretion in whole blood cell cultures treatedwith increasing concentrations (10-9 to10-6 M) of dexamethasone. Tumor-necrosisfactor-α (TNF-α), interleukin-6 (IL-6), andinterleukin-1β (IL-1β) were measured using specific immunoassays.Crohns disease patients had a markedly decreaseddexamethasone-mediated inhibition of TNF-α (P <0.01), IL-6 (P < 0.001), and IL-1β (P < 0.01) compared to healthy subjects, with a shift ofthe dexamethasone dose-response curve to the right. Nosignificant differences in the basal and LPS-stimulatedsecretion of the three cytokines were observed between CSD and non-CSD patients, and bothsubgroups of patients had similar degrees ofdexamethasone-mediated cytokine inhibition. We concludethat patients with Crohns disease have a significantdecrease in the corticosensitivity of their leukocytes.This may be related to a specific genetic/constitutionalbackground and/or could be acquired, due toinflammation-related endocrine and/or immunefactors.

Serum concentration of human chorionic gonadotropin and its alpha and beta subunits. 2. Trophoblastic tumours.

Using specific homologous radioimmunoassays of native hCG and its α and β subunits, we determined the levels of these glycoproteins in unfiltered maternal blood serially obtained in five non‐invasive hydatidiform moles before and after evacuation. Some of these samples were assayed after gel filtration chromatography on Sephadex G 100. Twelve samples, obtained in cases of invasive trophoblastic tumour after ablative surgery and chemotherapy, were also assessed for their hCG, hCGα and hCGβ content. In unaborted moles, mean circulating levels of native hCG and free hCGβ were considerably increased (seven and thirteen times, respectively) as compared to normal pregnancies of the same age, whereas levels of free hCGα were either normal or slightly elevated. Chromatographic analyses of molar sera confirmed the presence of free circulating subunits, and separated hCGβ in its monomeric form from its higher molecular weight form, the latter being in greater quantity than in normal pregnancy sera. In contrast, the elution profile of serum native hCG was comparable in cases of normal and molar pregnancy. Successful curettage was accompanied by a return to normal levels of the native hCG and its α and β subunits in 40–90 days. Persistence of tumour tissue was indicated by a slight increase in levels of native hCG and the β subunit. Determination of α subunit level was less useful for the detection of any relapse.

Immunoreactive prolactin like material in the urine of women

Immunoreactive prolactin-like material (Ir Prl) was detected in urines of eugonadal women during the luteal phase and in urines of pregnant and lactating women. The levels of Ir Prl urinary excretion per 24 h and of elimination per 100 ml of glomerular filtrate were highest in lactating women as compared to pregnant women; levels in pregnant women were elevated as compared to eugonadal subjects. Iv injection of thyrotropin releasing hormone (TRH, 200 μg) caused increased levels of urinary Ir Prl. The physicochemical characteristics of urinary Ir Prl of lactating women were investigated by filtrating urine samples on Ultragel Aca 54 in presence or absence of Trasylol. Urines, supplemented with Trasylol and analyzed either immediately or after storage at room temperature for 24 h, contained in addition to the 23,000 Mr monomeric form (25.2+7.4%), two fractions of high (≥ 70,000) or low (< 23,000) molecular weight, respectively. The latter material largely predominated (73.5±7.3%). Urines kept at room temperature for 24 h without Trasylol showed variable but significant decreases in the monomer form with a parallel increase in high MW and fragmented forms. The extent of degradation of the monomer was directly proportional to the proteolytic activity of the urines as estimated by the Azocoll breakdown test. Contrary to what was observed with the urinary endogenous monomeric Prl, human pituitary Prl.remained unaltered upon incubation in Trasylol-free urines up to 45 h. These experiments suggest that Prl when it is excreted in the urine, undergoes varying modifications which give rise to immunoreactive aggregates, fragments and a material of normal molecular weight but of high sensitivity to the action of the urinary proteases.