The human corpus luteum (CL) is a highly vascularized, temporarily active endocrine gland and consists mainly of granulosa cells (GCs), theca cells (TCs), and endothelial cells (ECs). Its cyclic growth and development takes place under the influence of gonadotropic hormones. If pregnancy does occur, human chorionic gonadotropin (hCG) takes over the function of luteinizing hormone (LH) and, in contrast to LH, extends the functional life span of the CL. In this study, we investigated the effects of hCG and LH in a spheroidal cell culture model of CL development. Our data indicate that GCs secrete factors under the control of hCG that increase sprout formation of EC-spheroids. We demonstrate that the most prominent of these factors is VEGF-A. Furthermore, we found that both LH and hCG decrease sprout formation of GC-spheroids. After forming EC-GC coculture spheroids and consequently bringing GCs and ECs in close contact, sprouting increased under the influence of hCG, however not under LH. These experiments provide evidence for an hCG dependent functional switch in the GCs after coming in contact with ECs. Moreover, it demonstrates the considerably different effects of hCG and LH on GCs although their signaling is transmitted via the same receptor.

Background Hyperalgesia that develops following nerve ligation corresponds temporally and in magnitude with the number of thalamic mast cells located contralateral to the ligature. We tested the possibility that mast cells modulate nociception centrally, similar to their role in the periphery. Methods We examined the central effect of two hyperalgesic compounds that also induce mast cell degranulation and stabilized mast cells using cromolyn. Results Thermal hyperalgesia (tail flick) induced by nerve growth factor (NGF, a neurotrophic compound) and mechanical hyperalgesia (von Frey) induced by dynorphin A (1–17) (opioid compound) each correlated with the percent of thalamic mast cells that were degranulated. Degranulation of these mast cells by the central injection of compound 48/80, devoid of neurotrophic or opioid activity, was sufficient to recapitulate thermal hyperalgesia. Stabilization of mast cells by central injections of cromolyn produced no analgesic effect on baseline tail flick or von Frey fiber sensitivity, but inhibited thermal hyperalgesia produced by compound 48/80 and tactile hyperalgesia induced by dynorphin and by Freund’s complete adjuvant. Finally, chemical nociception produced by the direct activation of nociceptors by formalin (phase I) was not inhibited by centrally injected cromolyn whereas chemical nociception dependent on central sensitization (formalin-phase II and acetic acid-induced abdominal stretches) was. Conclusions These convergent lines of evidence suggest that degranulation of centrally located mast cells sensitizes central nociceptive pathways leading to hyperalgesia and tonic chemical sensitivity.

No abstract

Since there are divergencies in the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) in old age, and since a hypothalamopituitary dysfunction has been suggested in the elderly, we have studied the thyroid function and the TRH responsiveness of TSH and prolactin (PRL) in 56 euthyroid patients over 70 years old, grouped according to age (70-79, 80-89, 90 or more years) and sex. Results were compared to those of 15 postmenopausal women and 11 men. In the elderly patients there was a decrease in plasma tri-iodothyronine (T3) and an increase in reverse T3 (rT3) levels while thyroxine (T4), basal TSH and PRL levels remained normal. The mean TSH and PRL responses to TRH (250 micrograms i.v.) were reduced but there was no age effect within the elderly. Only a sex effect was detected, TSH and PRL responses being appreciably lowered in men. In eight patients without severe disease or malnutrition, the response of TSH was not significant. We conclude that despite an apparent euthyroid status, TSH and PRL responses are blunted in elderly patients, and more in men than in women. These data, consistent with a hypothetical hypothalamopituitary dysfunction, indicate the difficulties of thyroid status assessment in the elderly.

No abstract