Serum FSH bioactivity and response to acute gonadotrophin releasing hormone (GnRH) agonist stimulation in patients with polycystic ovary syndrome (PCOS) as compared to control groups

OBJECTIVE We evaluated the biological activity of FSH in the serum of women with polycystic ovary syndrome before and after acute administration of a GnRH agonist as compared to control groups. DESIGN FSH, oestradiol and androstenedione response to buserelin (100 μg s.c.) comparing seven polycystic ovary patients, six idiopathic hirsute women, 11 normal women in the follicular phase and nine normal men. MEASUREMENTS Rat granulosa cell aromatase bioassay in the presence or absence of polyethyleneglycol (PEG) pretreated 2% serum. Serum biological FSH (B-FSH), immunological FSH (I-FSH) and B/I ratio at times 0,1, 2, 3, 4, 8, 12 and 24 hours. Serum androstenedione and oestradiol at times 0 and 24 hours. RESULTS Human gonadotrophin-free (oral contraceptive user and after FSH immunoabsorption) and PEG-pre-treated serum increases the aromatase activity in response to increasing doses of purified FSH. The maximum enzymatic activity is however higher with 2% serum than with 4% serum. The amplitude of the B-FSH response to the GnRH agonist is markedly decreased in the polycystic group as compared to the group of normal women. There is also a small decrease in the l-FSH response in the polycystic women. When compared to that of normal women, the area under the curve in the polycystic ovary patients is reduced by 71% for B-FSH (P<001) and by 23% for l-FSH (P<0.05). The B-FSH and I-FSH responses in men are very small. After an initial decrease the B/I ratio returns to baseline level in normal women but remains low in the other groups. At time 24 hours, there is no significant change in the serum concentration of androstenedione but serum oestradiol, the baseline of which is significantly higher in the polycystic patients than in normal women, is also significantly higher at 24 hours (P< 0.05) in response to the pharmacological release of FSH. CONCLUSION The gonadotrophin-free and PEG-pre-treated human serum has an inherent stimulatory effect on the rat granulosa aromatase bioassay with a higher activity at 2% serum. Acute GnRH agonist stimulation reveals a deficiency in the FSH response in polycystic ovary patients. The greater deficit in B-FSH than in l-FSH would indicate a possible modification in the FSH isoforms in this syndrome. The meaning of this observation for the understanding of the physiopathology of the polycystic ovary syndrome remains to be evaluated.     

Morphological variation of layer III pyramidal neurones in the occipitotemporal pathway of the macaque monkey visual cortex

We compared the morphological characteristics of layer III pyramidal neurones in different visual areas of the occipitotemporal cortical 'stream', which processes information related to object recognition in the visual field (including shape, colour and texture). Pyramidal cells were intracellularly injected with Lucifer Yellow in cortical slices cut tangential to the cortical layers, allowing quantitative comparisons of dendritic field morphology, spine density and cell body size between the blobs and interblobs of the primary visual area (V1), the interstripe compartments of the second visual area (V2), the fourth visual area (V4) and cytoarchitectonic area TEO. We found that the tangential dimension of basal dendritic fields of layer III pyramidal neurones increases from caudal to rostral visual areas in the occipitotemporal pathway, such that TEO cells have, on average, dendritic fields spanning an area 5-6 times larger than V1 cells. In addition, the data indicate that V1 cells located within blobs have significantly larger dendritic fields than those of interblob cells. Sholl analysis of dendritic fields demonstrated that pyramidal cells in V4 and TEO are more complex (i.e. exhibit a larger number of branches at comparable distances from the cell body) than cells in V1 or V2. Moreover, this analysis demonstrated that the dendrites of many cells in V1 cluster along specific axes, while this tendency is less marked in extrastriate areas. Most notably, there is a relatively large proportion of neurones with 'morphologically orientation-biased' dendritic fields (i.e. branches tend to cluster along two diametrically opposed directions from the cell body) in the interblobs in V1, as compared with the blobs in V1 and extrastriate areas. Finally, counts of dendritic spines along the length of basal dendrites revealed similar peak spine densities in the blobs and the interblobs of V1 and in the V2 interstripes, but markedly higher spine densities in V4 and TEO. Estimates of the number of dendritic spines on the basal dendritic fields of layer III pyramidal cells indicate that cells in V2 have on average twice as many spines as V1 cells, that V4 cells have 3.8 times as many spines as V1 cells, and that TEO cells have 7.5 times as many spines as V1 cells. These findings suggest the possibility that the complex response properties of neurones in rostral stations in the occipitotemporal pathway may, in part, be attributed to their larger and more complex basal dendritic fields, and to the increase in both number and density of spines on their basal dendrites.      

Functional, biochemical, and histopathologic consequences of high-dose interleukin-2 administration in rats

A variety of side effects have been reported with the use of interleukin-2 alone or in combination with lymphokine-activated killer cells in patients with disseminated neoplasms. The present study was undertaken to determine the effects of high-dose interleukin-2 administration in normal rats. Sprague-Dawley rats were treated with intravenous recombinant interleukin-2 (900,000 IU/kg/day) for 9 consecutive days. Animals were placed in individual metabolic cages, and arterial blood pressure, food intake, body weight, and urine output were monitored. On day 10, animals were killed by exsanguination, various tissues were harvested, and a variety of hematologic and chemical assays were performed. The results were compared with those of placebo-injected normal control and pair-fed groups. The interleukin-2-treated group exhibited anorexia, weight loss, hypotension, anemia, leukocytosis, lymphocytosis, eosinophilia, hypercalcemia, azotemia, and a marked urinary concentration defect. Histologic examination of various tissues revealed widespread infiltration with mono-nuclear cells and eosinophils in most organs, especially in the lungs and liver of interleukin-2-treated animals. Other abnormalities included severe panlobular hepatitis, hepatocellular necrosis, and thymic involution. Renal involvement was mild and consisted of focal interstitial infiltration by mononuclear cells. According to these observations, administration of high-dose interleukin-2 in normal rats results in a score of significant functional, biochemical, and histologic abnormalities.     

β-Endorphin/β-lipotropin release and gonadotropin secretion after acute exercise in physically conditioned males

Summary β-endorphin (β-EP) andβ-lipotropin (β-LPH) concentrations were measured in the basal state and after acute exercise for 15 min or until exhaustion in 6 physically conditioned male volunteers. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and prolactin were also measured in the basal state. In addition, the concentrations of the gonadotropins (LH and FSH) were determined after exercise and the gonadotropin response to gonadotropin releasing hormone was assessed before and after exercise. The data show that acute exercise stimulates the release of bothβ-EP andβ-LPH which return to base-line levels within 60 min after exercise. This is in contrast to our previously described results in physically unconditioned male volunteers in whom onlyβ-LPH release was noted after exercise. Serum LH concentrations declined after exercise reaching nadir values between 60 to 150 min after exercise. As we previously reported in physically unconditioned male volunteers, serum FSH concentrations did not change with exercise and the gonadotropin response to LRH stimulation was uninfluenced by exercise. Serum testosterone and prolactin concentration were within the normal range for healthy adult males. We speculate that the difference inβ-EP release with exercise in physically conditioned and unconditioned males represents a difference in processing of the opioid precursor molecule (pro-opiomelanocortin, POMC) in the two groups.     

Plasma concentrations of atrial natriuretic peptide, arginine vasopressin and hormones of the renin-angiotensin system in patients with end-stage renal disease

Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), plasma renin activity (PRA) and aldosterone, were measured before and after 3 h of hemodialysis in 9 patients with end-stage renal disease on maintenance hemodialysis. Hormone concentrations were also determined in the same patients on a separate occasion after 1 h of ultrafiltration (UF). Plasma concentrations of ANP were significantly higher in the patients with ESRD than in a normal reference population and declined after both 1 h and 3 h of hemodialysis. Plasma concentrations of ANP failed to exhibit a significant decline after 1 h of UF. Plasma AVP concentrations were not significantly different after either hemodialysis or UF, while plasma aldosterone concentrations fell with hemodialysis. The decline in plasma aldosterone concentrations paralleled the decrease in dialysis-induced fall in serum potassium concentrations. There was no correlation between the blood pressures, heart rate, interdialytic weight gain and estimated fluid overload and any of the hormones measured except for the plasma renin activity (PRA) which correlated significantly with the systolic blood pressure. The data suggest that ANP may not be a major factor in blood pressure regulation in normotensive patients with ESRD and its elevation in patients with ESRD is most likely due to fluid overload and atrial distention as well as a possible reduction in its metabolic clearance in renal insufficiency. The fall in plasma ANP following hemodialysis is not due to its removal by dialysis but is most likely due to a reduction in ANP production caused by dialysis-induced correction of hypervolemia.     

Heterogeneity of left ventricular segmental wall thickening and excursion in 2-dimensional echocardiograms of normal human subjects

Regional abnormalities of left ventricular (LV) wall thickening and excursion have been demonstrated by 2-dimensional (2-D) echocardiography. However, the variability of normal segmental contraction has not previously been defined. We performed 2-D echocardiography in 12 normal men aged 19 to 27 years. We obtained short-axis images at the level of the mitral valve, chordae tendineae, papillary muscles, and apex at end-diastole and end-systole. A computer-based system divided each short-axis image into 12 cavity and wall segments, and analyzed percent systolic wall thickening along each radius and percent area change of each cavity segment. Overall variability of contraction as well as the contributions of several sources of variability were determined. The overall range of cavity segment area change was 0 to 100% and of segmental wall thickening was 0 to 150% in these normal subjects. Average contraction was similar at different ventricular levels. Significant differences were found between adjacent segments at each level as well as between subjects. Intrathoracic cardiac rotation and motion were minimal; correction for these movements did not significantly alter the variability of contraction as calculated from 2-D echocardiograms. Temporal asynergy of contraction did contribute to variability; correction resulted in a significant alteration in mean segmental area change (from 59 ± 20% [standard deviation] uncorrected to 66 ± 16% corrected, p < 0.001) and in mean segmental wall thickening (58 ± 29% uncorrected to 71 ± 34% corrected, p < 0.01). Substantial interexamination variability also occurred with an average difference in cavity segment area change of 20% per segment and in segmental wall thickening of 29% per segment between 2 analyses by the same observer. Thus, considerable intersegmental and intersubject variability of LV contraction occurs in normal subjects as exhibited on 2-D echocardiograms, exaggerated by technical difficulties in analyzing and reproducing the echocardiographic tracings. Significant differences in segmental wall thickening and endocardial excursion may occur in adjacent segments in normal subjects, and therefore such differences alone may not indicate cardiac disease.