Interleukin-1 beta induces prostaglandin G/H synthase-2 (cyclooxygenase-2) in primary murine astrocyte cultures

Activation of glial cells and the consequent release of cytokines, proteins, and other intercellular signaling molecules is a well-recognized phenomenon in brain injury and neurodegenerative disease. We and others have previously described an inducible prostaglandin G/H synthase, known as PGHS-2 or cyclooxygenase-2, that is up-regulated in many cell systems by cytokines and growth factors and down-regulated by glucocorticoid hormones. In cultured mouse astrocytes we observed increased production of prostaglandin E2 (PGE2) after stimulation with either interleukin-1 beta (IL-1 beta) or the protein kinase C activator phorbol 12-myristate 13-acetate (TPA). This increase in PGE2 content was blocked by pretreatment with dexamethasone and correlated with increases in cyclooxygenase activity measured at 4 h. Northern blots revealed concomitant increases in PGHS-2 mRNA levels that peaked at 2 h and were dependent on the dosage of IL-1 beta. Dexamethasone inhibited this induction of PGHS-2 mRNA by IL-1 beta. TPA, basic fibroblast growth factor, and the proinflammatory factors tumor necrosis factor alpha and lipopolysaccharide, but not interleukin-6, also stimulated PGHS-2 mRNA expression. Relative to IL-1 beta, the greater increases in PGE2 production and cyclooxygenase activity caused by TPA correlated with a greater induction of PGHS-2 mRNA. Furthermore NS-398, a specific inhibitor of cyclooxygenase-2, blocked > 80% of the cyclooxygenase activity in TPA-treated astrocytes. These findings indicate that increased expression of PGHS-2 contributes to prostaglandin production in cultured astrocytes exposed to cytokines and other factors.     

Limbic system-associated membrane protein (LAMP) induces neurite outgrowth and intracellular Ca2+ increase in primary fetal neurons

The ability of cell adhesion molecules (CAMs) to transduce cell surface signals into intracellular responses is critical for developing neurons, particularly during axonal pathfinding and targeting. It has been suggested that different CAMs can promote neuronal outgrowth via activation of common neuronal CAM-specific second-messenger pathways, although the elements involved in this cascade could differ. Limbic system-associated membrane protein (LAMP), a member of the Ig superfamily, is a molecule that promotes cell adhesion and neurite outgrowth from specific populations of fetal neurons. In the present study, we show that LAMP can induce several types of calcium (Ca2+) signals. Neurite outgrowth is promoted if fetal hippocampal neurons are grown on lamp-transfected CHO cells. This LAMP-induced outgrowth of neurons is mediated in part through activation of L-type Ca channels. Application of soluble LAMP to cultures of fetal hippocampal neurons caused a sustained (up to 60 min) elevation of intracellular Ca2+ as measured by fluo-3 fluorescence on a confocal microscope. The number of responding hippocampal neurons was initially low, but increased with age in culture and the [Ca2+]i elevation was only partially decreased by an L-type Ca(2+)-channel blocker. In contrast, at all times in culture, only a small fraction of neurons from visual cortex responded to LAMP application and only with transient elevation of cytosolic Ca2+ (< 15 min). Based on these observations, LAMP appears to function primarily through homophilic interactions and acts in part by modulating intracellular Ca2+ levels during neurite outgrowth by increasing the Ca2+ influx through L-type calcium channels, but has additional effects on intracellular Ca2+ signaling at later developmental stages.     

Induction of metallothionein-I (MT-I) mRNA in primary astrocyte cultures is mediated by hypotonicity and not ethanol (EtOH) per se

Metallothionein (MT) mRNA was determined in rat astrocyte cultures in response to ethanol (EtOH). MT-I mRNA was significantly increased after 6 h exposure to isosmotic EtOH, but not hyperosmotic EtOH. Exposure to a hyposmotic/hypotonic solution also led to a significant increase in the expression of astrocytic MT-I mRNA. The large increase in MT-I mRNA was not due to removal of extracellular NaCl, because this effect was reversed by replacement of NaCl with N-methyl D-glucamine chloride. A significant decrease in MT-I mRNA was also noted in astrocytes exposed to an EtOH-free hyperosmotic/hypertonic solution. These results suggest (1) that EtOH per se does not directly induce MT-I mRNA expression, (2) that the induction by EtOH of MT-I mRNA is secondary to hypotonicity, and (3) that hyperosmotic/hypertonic exposure is associated with reduced expression of MT-I mRNA in astrocyte cultures.     

Effects of maturation on the phospholipid and phospholipid fatty acid compositions in primary rat cortical astrocyte cell cultures

Phospholipid and phospholipid fatty acid compositional changes were studied in rat cortical astrocytes during dibutyryl cyclic adenosine monophosphate (dBcAMP, 0.25 mM) treatment starting after 14 days in culture (DIC). After 15 DIC, ethanolamine- and choline glycerophospholipid levels were increased 1.2- and 1.3-fold, respectively in treated compared to control cells. However, after 21 and 28 DIC, these levels were not significantly different between groups. Both groups had an increase in phosphatidylserine levels with increasing time in culture. Similarly, ethanolamine plasmalogen levels were transiently elevated after 21 DIC, but returned to previous levels after 28 DIC. The phospholipid fatty acid compositions for the acid stable and labile ethanolamine- and choline glycerophospholipids indicated that in dBcAMP treated cells, 20:4 n-6 and 22:6 n-3 proportions were elevated with increasing time in culture relative to control cells. As 20:4 n-6 proportions increased, there was a concomitant decrease in 20:3 n-9 proportions, suggesting an up regulation of n-6 series elongation and desaturation. In contrast, in control cells, the 20:4 n-6 proportions decreased with a corresponding increase in the 20:3 n-9 proportions. Thus, in treated cells, the cellular phospholipid fatty acid composition was dramatically different than control cells, suggesting that dBcAMP treatment may act to increase fatty acid elongation and desaturation.     

Phenylarsine oxide, a tyrosine phosphatase inhibitor, induces an increase in the intracellular concentration of calcium in rat peritoneal macrophages and human fibroblasts]

Using Fura-2 microfluorimetry, phenylarsine oxide (PAO) (10-50 microM), a potent tyrosine phosphatase inhibitor, was shown to induce a dose-dependent increase in the free Ca2+ intracellular concentration in rat peritoneal macrophages and human foreskin fibroblasts. The PAO-induced increase in [Ca2+]i is not due presumably to depletion of intracellular Ca2+ stores but to mainly a stimulation of Ca2+ entry from the extracellular medium. This PAO-activated Ca2+ entry is attenuated by the following pharmacological agents. Organic and inorganic Ca2+ channel blockers: (nifedipine, verapamil and Ni2+); nonselective cation channel blocker niflumic acid; tyrosine kinase inhibitors genistein and methyl-2,5-dihydroxycinnamate; SH-reagents dithiothreitol parachloromercuribenzoate and N-ethylmaleimide; arachidonic acid metabolism inhibitors 4-bromophenacyl bromide, indomethacin and caffeic acid; microtubule disrupters vinblastine, colchicine and colcemide. On the contrary, microfilament disrupters, cytochalasin B and phalloidin, enhance PAO-activated Ca2+ entry. Our data suggest that the dynamic balance between tyrosine kinase and phosphatase activity may play a central role in the maintenance of homeostatic levels of [Ca2+]i both in unstimulated cells and after agonist application.     

Hydrocortisone induces an increase of amylase content in individual zymogen granules from rat pancreas

This study was performed to evaluate the effects of different doses of hydrocortisone (1, 10 and 25 mg/kg/day) administered for 1, 3 and 8 days on pancreatic enzyme storage in rats. The enzyme content in both pancreas homogenates and in individual isolated zymogen granules (ZGs) was measured using standard biochemical assays and flow cytometry, respectively. Hydrocortisone did not alter the total amount of pancreatic DNA but increased the pancreas enzyme content in a time-dose-dependent way. Amylase activity was significantly increased after hydrocortisone administration at day +8 when 10 mg/kg/day was used, and from the first day of treatment when 25 mg/kg/day was administered. A significant increase in trypsin activity was also observed in response to 25 mg/kg/day of hydrocortisone but only from the third day of treatment onwards. As compared with control rats, chronic administration of either 1 or 10 mg/kg/day of hydrocortisone did not alter significantly either the size or the percentage of the two ZG subpopulations (Z1 and Z2) identified in the pancreas by flow cytometry; in addition, no significant changes were observed in the mean amylase content per individual granule, although its mean concentration increased in rats treated with 10 mg/kg/day for 3 and 8 days. Nevertheless, when 25 mg/kg/day of hydrocortisone were administered for 1 and 3 days, a significant increase in the proportion of Z1 ZGs was observed, which may be related to the formation of new and smaller ZGs. When a very high dose of hydrocortisone (25 mg/kg/day) was used, an overall increase in the pancreatic enzyme content related to an increase in the mean amylase content per individual ZG was observed; this effect was apparent from the first day of treatment in the Z1 subset of ZGs and from day +3 in the Z2 subpopulation. Only a high concentration of hydrocortisone was able to alter the enzyme storage process in individual zymogen granules, but they maintain a normal enzyme load at lower hydrocortisone doses.     

Effect of osmolality and myo-inositol deprivation on the transport properties of myo-inositol in primary astrocyte cultures

myo-Inositol uptake measured in primary astrocyte cultures was saturable in the presence of Na+ with a Km of 13-18 microM and a Vmax of 9.4 nmoles/mg protein/hour in myo-inositol-fed cells, indicating a high affinity transport system. In myo-inositol-deprived cells, Km was about 53 microM with a Vmax of 13.2 nmoles/mg protein/hour. Decreasing osmolality decreased the Vmax to about 1.9 nmoles/mg protein/hour whereas increasing osmolality increased Vmax about 5-fold, while Kms were essentially unchanged in myo-inositol fed cells. In cells deprived of myo-inositol, Vmax decreased in hypotonic medium and increased in hypertonic medium almost 10-fold, but with more than a doubling of the Km regardless of the osmolality. Glucose (25 mM) inhibited myo-inositol uptake 51% whereas the other hexoses used inhibited uptake much less. Our findings indicate that myo-inositol uptake in astrocytes occurs through an efficient carrier-mediated Na(+)-dependent co-transport system that is different from that of glucose and its kinetic properties are affected by myo-inositol availability and osmotic stress.     

Endothelin-1 induces cholestasis which is mediated by an increase in portal pressure

Endothelin-1 (ET-1) is a potent vasoactive peptide which generally exerts its effect on target cells by increasing [Ca++]i. Both vasoconstriction (resulting in an increase in perfusion pressure) and increased [Ca++]i are actions of ET-1 that may result in cholestasis. Single-pass isolated perfused rat liver (IPRL) were used, and [Ca++]i was measured in both populations of hepatocytes and single cells. ET-1 (0.1-100 nM) induced a dose-dependent increase in perfusion pressure and decrease in bile flow. Perfusion pressure increased by 112% (p < 0.001) and bile flow decreased by 17% (p < 0.008) in response to 2 nM ET-1. At this concentration of ET-1, but not at higher concentrations, the cholestasis was abolished (p > 0.18 vs basal) and the rise in perfusion pressure was decreased (by 62%; p < 0.002) by the vasodilator papaverine. This ET-1 concentration also had no measurable effect on [Ca++]i in isolated hepatocytes. Taken together these findings indicate that ET-1 inhibits bile flow in IPRL and suggests that this effect is mediated by vasoconstriction and not by changes in hepatocyte cytosolic Ca++.     

Human immunodeficiency virus type 1 Tat protein induces death by apoptosis in primary human neuron cultures

Hamartomas are rare benign tumors appearing very often without any symptoms. In case of diagnostic detection the operative exploration is indicated for a correct histological diagnosis and resection. In this report we describe a very rare case of mesenterial hamartoma. During the late postoperative course a refilling chylothorax and chylous ascites occurred. With total parenteral nutrition, excluding short- and long-chain fatty acids, chylous leakage was successfully treated. The chylous exudation was stopped totally; only intraabdominally did minimal ascites persist. The therapy was continued by a oral Ceres diet nutrition. The conservative therapy involving total parenteral nutrition permitted us to avoid the peritoneovenous Le Veen shunt and the associated complications.     

Inhibition of peroxisomal degradation by 3-methyladenine (3MA) in primary cultures of rat hepatocytes

BACKGROUND: A significant reduction in peroxisomes has been demonstrated in primary cultures of rat hepatocytes. This report demonstrates that 3-methyladenine (3MA), a potent inhibitor of autophagy, inhibits this effect. METHODS: Hepatocytes from male Wistar rats were isolated by a two-step in situ perfusion technique using collagenase and were cultured in Williams E medium. After a 2-hr attachment period (day 0 of culture), the cells were treated with 200 microM bezafibrate (BF), a peroxisome proliferator, and 5 mM 3MA for 3 days. The cells in the culture dish were fixed in situ, stained for catalase, and embedded in Poly/Bed 812. The number and size of peroxisomes in electron micrographs were analyzed morphometrically. RESULTS: After 3 days of culture, the number of peroxisomes had decreased to 30% of the day 0 level. However, the day 0 level was maintained by treatment with 3MA. In BF-treated cells, many autophagosomes were observed, and peroxisomes had proliferated significantly, although they did not exceed the day 0 level. In cells treated with a combination of 3MA and BF, the number and size of peroxisomes had increased remarkably. CONCLUSIONS: These results suggest that 3MA is effective in maintaining both the number and size of peroxisomes in the course of primary cultures of rat hepatocytes. Suppression of peroxisome proliferation by treatment with BF may be regulated by autophagic/lysosomal degradation.     

Interactions between metallothionein inducers in rat liver and primary cultures of rat hepatocytes

The interaction of Zn, stress and endotoxin on liver metallothionein (MT) regulation has been studied in the rat. Zn, stress and endotoxin increased liver MT levels significantly, by 12-, 5- and 8-fold, respectively. The previous administration of Zn to stress or endotoxin treatments increased MT levels by 35- and 42-fold, respectively, indicating a synergistic effect in both cases. In contrast, when liver MT was preinduced by stress, MT levels were further increased by endotoxin only in an additive manner. In another experiment where liver MT induction by stress was studied in control rats and in rats with preinduced MT by Zn, endotoxin or stress, it was found that Zn pretreated animals had higher MT-I mRNA levels than endotoxin- or stress-pretreated ones. No synergisms between dexamethasone, Zn, TNF and IFN were observed in primary culture of hepatocytes. These results suggest that the observed synergisms between Zn and other MT inducers in vivo in the liver is a consequence of increased Zn levels in the body and mobilization capacity, with concomitant MT synthesis.     

Glucocorticoids increase retinoid-X receptor alpha (RXRalpha) expression and enhance thyroid hormone action in primary cultured rat hepatocytes

A dynamic model of glucose overflow metabolism in batch and fed-batch cultivations of Escherichia coli W3110 under fully aerobic conditions is presented. Simulation based on the model describes cell growth, respiration, and acetate formation as well as acetate reconsumption during batch cultures, the transition of batch to fed-batch culture, and fed-batch cultures. E. coli excreted acetate only when specific glucose uptake exceeded a critical rate corresponding to a maximum respiration rate. In batch cultures where the glucose uptake was unlimited, the overflow acetate made up to 9. 0 +/- 1.0% carbon/carbon of the glucose consumed. The applicability of the model to dynamic situations was tested by challenging the model with glucose and acetate pulses added during the fed-batch part of the cultures. In the presence of a glucose feed, E. coli utilized acetate 3 times faster than in the absence of glucose. The cells showed no significant difference in maximum specific uptake rate of endogenous acetate produced by glucose overflow and exogenous acetate added to the culture, the value being 0.12-0.18 g g-1 h-1 during the entire fed-batch culture period. Acetate inhibited the specific growth rate according to a noncompetitive model, with the inhibition constant (ki) being 9 g of acetate/L. This was due to the reduced rate of glucose uptake rather than the reduced yield of biomass.     

Neural cell adhesion molecule (N-CAM) domains and intracellular signaling pathways involved in the inhibition of astrocyte proliferation

The neural cell adhesion molecule (N-CAM) inhibits astrocyte proliferation in vitro and in vivo, and this effect is partially reversed by the glucocorticoid antagonist RU-486. The present studies have tested the hypothesis that N-CAM-mediated inhibition of astrocyte proliferation is caused by homophilic binding and involves the activation of glucocorticoid receptors. It was observed that all N-CAM Ig domains inhibited astrocyte proliferation in parallel with their ability to influence N-CAM binding. The proliferation of other N-CAM-expressing cells also was inhibited by the addition of N-CAM. In contrast, the proliferation of astrocytes from knockout mice lacking N-CAM was not inhibited by added N-CAM. These findings support the hypothesis that it is binding of soluble N-CAM to N-CAM on the astrocyte surface that leads to decreased proliferation. Signaling pathways stimulated by growth factors include activation of mitogen-activated protein (MAP) kinase. Addition of N-CAM inhibited MAP kinase activity induced by basic fibroblast growth factor in astrocytes. In accord with previous findings that RU-486 could partially prevent the proliferative effects of N-CAM, inhibition of MAP kinase activity by N-CAM was reversed by RU-486. The ability of N-CAM to inhibit astrocyte proliferation was unaffected, however, by agents that block the ability of N-CAM to promote neurite outgrowth. Together, these findings indicate that homophilic N-CAM binding leads to inhibition of astrocyte proliferation via a pathway involving the glucocorticoid receptor and that the ability of N-CAM to influence astrocyte proliferation and neurite outgrowth involves different signal pathways.     

PEDF (pigment epithelium-derived factor) promotes increase and maturation of pigment granules in pigment epithelial cells in neonatal albino rat retinal cultures

AIMS: To clarify the association of p53 and CD34 expression with development of malignant solitary fibrous tumour we have studied 10 cases of solitary fibrous tumour arising in the pleura, retroperitoneum and pelvic cavity with clinicopathological features of malignancy. METHODS AND RESULTS: Tumours were localized solid masses with or without necrosis in eight and they nearly totally occupied the pleural cavity in two. Basic histology of the tumours was the proliferation of spindle cells arranged in 'patternless' pattern or in interlacing bundles with nuclear atypia and mitotic activities of various degree. In two, high-grade foci were present within low or intermediate-grade tumours. Recurrent tumours also showed more atypical features than primary tumours in two. Immunohistochemical studies showed CD34 positivity in seven, but three of them showed marked diminution or complete loss of CD34 expression in high-grade foci or a recurrent tumour. Three high-grade cases showed totally negative staining for CD34. p53 was strongly expressed in cases with fatal outcome, clinical recurrence, nuclear atypia, high mitotic activity or local invasion, whereas almost negative in benign tumours. CONCLUSIONS: Malignant solitary fibrous tumours may occur de novo or by transformation within benign or low-grade tumours and may be associated with p53 mutation. Although CD34 is a useful marker in the diagnosis of solitary fibrous tumour, one should bear in mind that its expression can be lost in high-grade tumours.     

Inhibition of (Na/K)-ATPase by NFE induces an increase in mechanical activity of perfused guinea-pig heart

The effect of 1-(5-nitro-2-furyl)-2-(phenylsulfonyl)-2-(furylcarbonyl)- ethylene (NFE) on stimulation of (Na/K)-ATPase by sodium and potassium ions was tested in isolated, partially purified sarcolemmal preparation from guinea-pig hearts. NFE inhibited competitively the stimulation of the enzyme by increasing concentrations of potassium. This inhibition was characterized by a significant (p < 0.001) increase of the K0.5 value, a considerable decrease of the Hill's cooperativity constant n as well as by an insignificant diminution of the Vmax value. Contrary to the effect on stimulation by potassium, NFE inhibited non-competitively the stimulation of the ATPase by sodium ions with a significant (p < 0.001) depression of Vmax but without any considerable effect on the K0.5 and n values. These results indicated that NFE may interact with the molecule of (Na/K)-ATPase in a locus close to or identical with the potassium binding site of the enzyme, i.e., in a similar mode as it was well documented for ouabain. This possibility was strongly supported by the finding that NFE administered at the concentration of 0.1 mumol/l in the perfusion medium increased significantly (p < 0.01) the mechanical activity of isolated perfused guinea-pig heart (Langendorff preparation). Nevertheless, it also caused some adverse effects such as a slight increase in coronary flow resistance and in heart rate as well as in the left ventricular end-diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of rat hepatic 3 alpha-hydroxysteroid dehydrogenase in vivo and in primary cultures of rat hepatocytes

Lamoids in North America harbor a wide variety of parasites. Treatment and control methods based on previous experience with parasites of cattle and sheep have been successful, but problems do exist. First, the pharmacokinetics for most anthelmintics have not been evaluated in llamas. Second, even though llamas, sheep, and cattle share many parasites, the two most common nematodes found in llamas (C. mentulatus and T. tenuis) are not part of the parasitic fauna of livestock. This presents difficulties in basing treatment and control methods on those recommended for cattle and sheep. Variability in host response to the same parasite also hinders the use of cattle and sheep as models for the llama. This is best demonstrated by F. magna and F. hepatica; the reaction induced by the first more closely resembles those seen in cattle than sheep, but the reaction induced by the second more closely resembles those seen in sheep than cattle. Finally, parasites known to be pathogenic in livestock (e.g., N. battus) have unknown effects in llamas. These examples illustrate that we must use caution when extrapolating existing knowledge regarding the parasites of sheep and cattle to llamas. Further research on the epidemiology of parasites peculiar to the llama is needed to enhance control efforts. Improved methods of diagnosis and treatment of parasites also are areas in which further efforts are needed.     

Inhibition of sphingolipid biosynthesis in rat primary hepatocyte cultures by fumonisin B1 and other structurally related compounds

Plaque cholesterol is thought to be derived exclusively from low-density lipoproteins that have become trapped and modified in the subendothelial space of arterial vessels. However, in this study we provide the first visual evidence that demonstrates that (a) remnants of post-prandial lipoproteins rapidly penetrate arterial tissue; (b) efflux is not complete; and (c) focal accumulation of chylomicron remnants occurs within the subendothelial space. The arterial retention of chylomicron remnants is consistent with atherogenesis being in part a post-prandial phenomenon.     

Inhibition of transforming growth factor-beta1 and UV light-induced apoptosis by prostanoids in primary cultures of rat hepatocytes

Treatment of rat hepatocytes cultured in collagen gel with transforming growth factor-beta1 (TGFbeta1) or with UV light strongly increased the frequency of apoptotic nuclei within 24 h; at doses of 0.5 ng/ml TGFbeta1 or 90 J/m2 UV light about 17 and 22% apoptotic nuclei were determined, respectively. DNA of the treated cells showed internucleosomal DNA fragmentation. Already the presence of the cytokine for only 1 h significantly induced apoptosis. The prostanoids PGI2, PGD2, and PGE1 decreased the frequency of apoptotic nuclei in a dose-dependent manner by up to 70 to 80% and suppressed internucleosomal DNA fragmentation. In contrast, PGE2 and PGF2alpha elicited a smaller protective effect and arachidonic acid had none. In the case of PGE1 it was shown that the prostaglandin was most effective when added together with TGFbeta1 or within 2 h before or after treatment with this cytokine. An early increase of the tumor suppressor gene product p53 is thought to play a decisive role in UV light-induced apoptosis. However, this increase in p53 was not affected by the strong cytoprotective prostacyclin PGI2. Our findings show a marked antiapoptotic activity of the prostanoids PGE1, PGI2, and PGD2 and raise the question of whether these prostanoids may influence apoptosis in pathological processes in the liver.     

Differential regulation of leucine-rich primary response gene 1 (LRPR1) mRNA expression in rat testis and ovary

In immature rat Sertoli cells, leucine-rich primary response gene 1 (LRPR1) represents a follicle stimulating hormone (FSH)-responsive gene; the function of the encoded protein is not yet known. LRPR1 mRNA expression is up-regulated very rapidly and specifically by FSH, both in cultured Sertoli cells and in vivo in regulation in more detail, in testis and ovary of fetal, immature, and adult rats. In addition, we have studied the expression of FSH receptor (FSHR) mRNA in relation to LRPR1 mRNA expression. In rat testis, LRPR1 mRNA and FSHR mRNA followed a similar expression pattern, during postnatal development and also at different stages of the spermatogenic cycle in the adult rat. Furthermore, after short-term challenge of the FSH signal transduction pathway in intact immature rats by injection with a relatively high dose of FSH, an inverse relationship between LRPR1 mRNA (up-regulation) and FSHR mRNA expression (down-regulation) was observed. Similar studies in the ovary provided completely different results. LRPR1 mRNA in the postnatal ovary is present well before expression of FSHR mRNA can be first detected. In addition, incubation of ovaries of immature rats with FSH or dibutyryl cyclic AMP (dbcAMP) did not result in up-regulation of LRPR1 mRNA expression. During fetal development, the LRPR1 mRNA expression pattern involved many more tissues, in contrast to the relatively tissue-specific expression of LRPR1 mRNA in gonads of 21 day old and adult rats. Moreover, LRPR1 mRNA expression could be detected as early as 12.5 days post-coitum, whereas FSHR mRNA is absent at this stage of fetal development. We concluded that the pronounced regulation of LRPR1 by FSH observed in the immature rat testis does not occur in the ovary. Furthermore, in the ovary LRPR1 mRNA expression does not appear to be dependent on FSH action. Finally, the LRPR1 gene product may play a general role during fetal development.