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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Testicular peritubular cells produce a paracrine factor termed PModS that has dramatic effects on Sertoli cell function in vitro. The current study was designed to examine the actions of PModS and hormones on Sertoli cell aromatase activity and plasminogen activator production at various stages of pubertal development. Sertoli cells were isolated from 10-, 20-, and 35-day-old rats (ages correspond to prepubertal, midpubertal, and late-pubertal stages of development). Aromatase activity was found to be high and hormone-responsive in prepubertal Sertoli cells and to decline and be nonresponsive to hormones in late-pubertal Sertoli cells. FSH was the only hormone found to influence aromatase activity and estrogen production. PModS alone was not found to affect aromatase activity at any of the developmental stages examined. Interestingly, PModS was found to suppress the ability of FSH to stimulate aromatase activity and estrogen production in midpubertal Sertoli cells. Results imply that PModS may promote Sertoli cell differentiation to a more adult stage of development that is less responsive to FSH in stimulating aromatase activity. In contrast to aromatase activity, plasminogen activator production was found to increase during pubertal development. Production of Sertoli cell tissue-type plasminogen activator (tPa) was stimulated by FSH at each of the developmental stages examined, whereas production of urokinase-type plasminogen activator (uPa) was influenced by FSH only in prepubertal Sertoli cells. Insulin also stimulated uPa and tPa production by prepubertal Sertoli cells, and retinol significantly suppressed uPa production and the ability of FSH to stimulate tPa production by midpubertal Sertoli cells.
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PMID:Developmental regulation of Sertoli cell aromatase activity and plasminogen activator production by hormones, retinoids and the testicular paracrine factor, PModS. 157 55

Pro-opiomelanocortin-derived peptides, alpha-MSH and beta-endorphin, are synthesized and secreted by Leydig cells, and are believed to have paracrine effects on Sertoli cells in the testis. Peptides with MSH activity stimulate adenylate cyclase and cAMP accumulation in Sertoli cell-enriched cultures. The purpose of the present study was to determine whether such peptides would affect Sertoli cell parameters, such as aromatase and plasminogen activator activities, that are known to be regulated by cAMP. alpha-MSH stimulated aromatase activity in Sertoli cell-enriched cultures prepared from 10-day-old rats and this effect was potentiated by methyl isobutylxanthine (MIX). The combination of alpha-MSH plus MIX was not as potent as FSH. alpha-MSH, des-acetyl-alpha-MSH, beta-MSH, ACTH(1-13), and ACTH(1-24) stimulated aromatase activity to a similar extent, suggesting that Sertoli cells do not distinguish between the activities of these peptides. alpha-MSH potentiated the action of dbcAMP and forskolin on Sertoli cell aromatase, but unexpectedly had no effect on the action of either half-maximal or maximal doses of FSH. The regulation of plasminogen activator was examined next; urokinase was markedly suppressed by FSH in 10-day-old Sertoli cells. Although neither alpha-MSH nor MIX alone had an effect on urokinase secretion, in combination they were as effective as FSH. In 10-day-old Sertoli cells each of these peptides had little or no effect on tissue plasminogen activator.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Estradiol and plasminogen activator secretion by cultured rat Sertoli cells in response to melanocyte-stimulating hormones. 247 57

1. Regulatory mechanism of cell growth of endometriosis in comparison with endometrium. Estradiol alone has no growth-promoting effect on both endometriotic and endometrial cells. Epidermal growth factor (EGF) stimulates cell growth of both cell types. Endometrial cells but not endometriotic cells produce and release EGF into culture media so that stimulatory effect of exogenous addition of EGF is blunted in endometrial cells. Estradiol exerts its mitogenic action by enhancing the mitogenic effect of EGF in endometrium. By contrast, the effect of estradiol is minimal in endometriotic cells, showing less dependency on estradiol for their proliferation. Progesterone inhibits cell growth of the both cell types in the same manner. 2. A biological role of EGF in endometriosis. Endometriotic cells possess EGF receptors. The affinity of the receptor is the same as that of endometrial cells. However, the number of receptor per cell is about half of that for endometrium. Estradiol increases the number of EGF receptors in endometrial cells which may explain the mitogenic effect of estradiol in the face of EGF. However, stimulatory effect of estradiol for EGF receptors is less pronounced in endometriotic cells. Mitogenic action of EGF is suggested to be mediated by phosphorylation of tyrosine residues of 170 kd protein in the tissues. EGF increases the production of tissue plasminogen activator (t-PA) and activates the aromatase activity of the both cell types. However, the stimulatory action of EGF on progestin receptor is observed only in endometrial cells. 3. Biochemical characterization of endometriotic cells in comparison with endometrial cells. Endometriotic tissues accumulate less amount of glycogen and XIII factor of blood coagulation as compared to endometrial tissues. The ability of endometriotic cells to release prostaglandin is also weaker, suggesting suppressed differentiated function of endometriotic cell. Endometriotic cells produce the same amount of CA125 as endometrial cells. Danazol and EGF inhibit the release of CA125 into culture media when standardized per cell. Therefore, normalization of CA125 levels during the treatment dose not always mean the reduction of the lesions but reflect the suppressed function of the endometriotic tissues. 4. Altered microenvironment of endometriotic tissues. An analysis of peritoneal fluid. The amount of peritoneal fluid (PF) with endometriosis increased throughout the menstrual cycle. A number of macrophage is reported to increase in PF with endometriosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Fundamental and clinical studies on biochemical properties of endometriosis in comparison with endometrium]. 250 2

Gonadotropin-releasing hormone (GnRH), in addition to its classical releasing action at the pituitary level, acts on multiple extrapituitary sites to regulate various reproductive functions. In the rat ovary, specific high affinity GnRH receptors have been identified in granulosa and theca cells. These binding sites mediate the inhibitory effects of GnRH and its agonists on gonadotropin-stimulated estrogen, progestin and androgen biosynthesis. At the granulose cell level, GnRH treatment decreases aromatase activity as well as the biosynthesis of pregnenolone and progesterone via inhibition of cholesterol side-chain cleavage and 3 beta-hydroxysteroid dehydrogenase enzymes. High concentrations of GnRH also stimulate low but significant levels of various steroids. In addition, treatment with high concentrations of GnRH induces ovulation and oocyte maturation in hypophysectomized rats. This is associated with the ability of GnRH to stimulate plasminogen activator activity in cultured granulosa cells. In the rat testis, GnRH receptors have been identified in Leydig but not Sertoli cells. Treatment with GnRH inhibits gonadotropin-stimulated androgen biosynthesis by the cultured Leydig cells. The inhibitory effect of GnRH on testicular androgen production occurs at sites distal to the formation of cyclic AMP and pregnenolone and may be due to decreases in the activity of the enzyme 17 alpha-hydroxylase and 17-20 desmolase. Since hypothalamic GnRH is unlikely to act at the gonadal level, several laboratories have attempted to isolate gonadal GnRH-like peptide which may serve as the ligand for specific gonadal GnRH receptors. Although the presence of ovarian GnRH-like substance still remains elusive, testicular GnRH-like substance has been identified. This gonadal peptide(s) may be an important local paracrine hormone. In addition to its action at the gonadal level, GnRH or GnRH-like peptides may play an important role as a neurotransmitter in the central nervous system. Exogenous administration of GnRH in selected brain areas has been shown to modulate sexual behavior in experimental animals, while neural pathways containing GnRH-like immunoreactive substances have been identified in several brain areas. We have recently synthesized a bioluminescent GnRH analog capable of serving as a specific GnRH ligand for a bioluminescent ligand receptor assay which is more sensitive than classical 125I-ligand assays. We have identified GnRH receptors in small, discrete brain regions. Thus, GnRH and GnRH-like peptides may play important paracrine and neurotransmitter roles in the regulation of various reproductive functions in extra-pituitary sites.
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PMID:Gonadotropin-releasing hormone as a paracrine hormone and neurotransmitter in extra-pituitary sites. 286 49

As stated earlier, the mammalian ovary maintains the continuous development of follicles, but only a few are selected to ovulate and form corpora lutea. These processes are regulated primarily by the gonadotropins and involve specific, sequential changes in the function of theca cells and granulosa cells. Data from recent studies (summarized in Figure 3) show that specific genes are turned on or off at different stages of follicular growth in response to estradiol and different amounts of gonadotropins and cAMP. For example, mRNA for RII51 in granulosa cells and theca cells increases in association with small increased in cAMP but is markedly reduced by the LH surge and high cAMP. The content of mRNA for other kinase subunits, RI and C alpha, show little or no change during similar hormonal changes. In theca cells, mRNA for 17 alpha-hydroxylase increased and decreased in a manner similar to that for RII51. In contrast, levels of mRNA for P450scc increased only gradually in follicles but were markedly increased by the LH surge and high concentrations of cAMP and then appeared to be constitutively expressed in rat corpora lutea in a cAMP-independent manner. PGS and t-PA appear to follow yet another pattern: rapid induction by the LH surge followed by a rapid decline in association with ovulation. One major task for reproductive endocrinologists and molecular biologists now is to determine how low and high concentrations of cAMP act to turn on and turn off the expression of these specific genes at specific times during follicular maturation. A working model of the molecular events occurring in theca and granulosa cells of PO follicles is shown in Figure 4. LH acts on theca cells via cAMP ro regulate both P450scc and P450(17) alpha mRNA levels, leading to increased biosynthesis of androstenedione. The mechanisms by which cAMP acts in theca cells remain to be determined but appear to involve an increase in the content of RII51, P450scc, and P450(17) alpha. In granulosa cells, androstenedione is converted to estradiol by the aromatase P450 enzyme system. Estradiol, in turn, binds to estradiol receptors present in these cells and may thereby regulate gene expression. However, despite the presence of estradiol and estradiol receptors, little or no effect of estradiol is observed unless FSH acts via the FSH receptor to increase intracellular concentrations of cAMP. In a manner not yet understood, cAMP appears to enhance the actions of estradiol.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Molecular aspects of hormone action in ovarian follicular development, ovulation, and luteinization. 328

The FSH activity in equine (e) FSH, eLH, eCG, and ovine LH were examined and compared to that in the standard reference preparation NIH FSH-S13 by three types of assay: the FSH radioreceptor assay with rat testicular homogenate and the stimulation of plasminogen activator production and steroidogenic activity in granulosa cells from diethylstilbestrol (DES)- or eCG-primed donor rats. The difference in the two types of granulosa cells was that the eCG-primed cells have already acquired significant aromatase activity. With the exception of oLH, which showed very little FSH activity (approximately 0.03-0.08 X NIH FSH-S13) throughout the three assays, the equine gonadotropins exhibited great variations in activity with respect to each assay. eFSH, the most active molecule in these assays, had an activity of 44 X NIH FSH-S13 in the receptor binding assay, 8.75 X NIH FSH-S13 in plasminogen activator production, and 4-5 X NIH FSH-S13 in steroid production when assayed in the DES-primed granulosa cells. In the eCG-primed cells, eFSH showed an activity of 4.2 X NIH FSH-S13 in plasminogen activator production and 8.2 X NIH FSH-S13 in progesterone production. eLH had an activity of 10 X NIH FSH-S13 in FSH radioreceptor assay, but showed very little activity and behaved like oLH in stimulation of the cellular responses of DES-primed granulosa cells. However, when eLH was assayed in the eCG-primed cells, it did show stimulating activity with respect to the production of plasminogen activator and progesterone; however, the dose-response curves were not parallel to those of eFSH and eCG. eCG had much less FSH receptor-binding activity (0.29 X NIH FSH-S13) than eLH. It behaved like a LH molecule in DES-primed granulosa cells, but did show activity (approximately 1 X NIH FSH-S13) in stimulating the production of plasminogen activator and progesterone in eCG-primed granulosa cells. From these results, we conclude that under our culture conditions, neither eLH nor eCG was active in the DES-primed granulosa cells, but both were active in the eCG-primed cells, and that the choice of assay conditions and reference standards is very important. Different types of assay may give rise to completely different comparisons for the same molecules. The equine gonadotropins provide a particularly dramatic example of such differences.
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PMID:Priming procedure and hormone preparations influence rat granulosa cell response. 391 55

The main emphasis of this paper is on the changes in function of granulosa cells as they undergo cytodifferentiation in follicles developing from the preantral to the antral stage, and on the hormones present in the milieu of gonadotrophins and steroids which are essential for these events to proceed normally. We found that FSH alone could induce aromatase activity in cultures of immature granulosa cells and that this effect could be duplicated by dibutyryl cyclic AMP. Incubation of cell sonicates under optimal conditions indicated that FSH acted on granulosa cells to increase the cellular concentration of active aromatase. Prior treatment with androgens augmented the FSH effect. Progesterone synthesis is another differentiated function which can be induced in culture by FSH alone and augmented in the presence of androgens. In assessing the enzymes involved in progesterone synthesis we found that cholesterol side-chain cleavage activity had similar hormonal requirements whereas 3 beta-hydroxysteroid dehydrogenase activity was stimulated by FSH alone. FSH also stimulates cyclic AMP binding activity in cultured granulosa cells during cytodifferentiation. These proteins represent another class of intracellular proteins, quite distinct from the steroidogenic enzymes, which increase as the granulosa cells mature. The ability of FSH to induce the appearance of LH and prolactin receptors, and stimulate the secretion of plasminogen activator and proteoglycans is reviewed. It is concluded that the appearance of steroidogenic enzymes and other intracellular proteins, cell-surface and secreted proteins as well as morphological maturation of granulosa cells require the presence of FSH. In the "turning-on" of some of these differentiated functions androgens play a permissive role. Having established events which occur during normal development of the follicle, we considered ways by which this overall process could be interrupted and fertility controlled. Here we describe the ways by which prolactin and LHRH interfere with the normal process of granulosa cell cytodifferentiation.
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PMID:Hormonal interactions in the control of granulosa cell differentiation. 631 Feb 32

The Sertoli cell has been shown to secrete a number of compounds, some of which are postulated to serve as chemical signals to the neighbouring cells. The evidence for such communication between Sertoli cells and Leydig cells is briefly summarized. More emphasis is put on Sertoli cell-germ cell interactions. The morphological observations do not support a direct transfer of material from cell to cell. Therefore, the observed dependency of germ cells on Sertoli cells and vice versa must be explained by diffusion of substances from one cell to the other. Examples of Sertoli cell secretory products whose production is dependent on the type of surrounding germ cells are ABP, plasminogen activator, a somatomedin-like compound, transferrin and a high-molecular weight aromatase inhibitor.
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PMID:Chemical messengers between Sertoli cells and neighbouring cells. 668 94

The abilities of LHRH and a potent LHRH agonist ([D-Ser-(But),6, des-Gly-NH210]LHRH ethylamide) inhibit FSH responses by rat granulosa cells and Sertoli cells in vitro have been compared. Granulosa cells isolated from 22- or 25-day-old diethylstilbestrol-primed rats and cultured under defined conditions for 48 h with NIH-FSH-S13 (300 ng/ml) or cholera toxin (0.1 microgram/ml) showed increased aromatase activity, as determined by the release of 3H2O from [1 beta-3H]testosterone. LHRH (10(-7) M) or th agonist (10(-8) M) added simultaneously with FSH or cholera toxin inhibited the effects on the release of 3H2O without influencing the protein content of the cell cultures. A smaller stimulation of 3H2O production occurred with (Bu)2cAMP (1.0 mM) plus 3-isobutyl-l-methylxanthine (0.1 mM), and this was partially suppressed in the presence of LHRH or the agonist. Parallel studies with Sertoli cells from 15- or 20-day-old rats demonstrated that culture under appropriate conditions with FSH, cholera toxin, or (Bu)2cAMP (0.5 mM) for 24 h caused an increase in cellular aromatase activity and enhanced secretion into the medium of plasminogen activator. However, no inhibition by LHRH (10(-7) or 10(-9) M) or the agonist (10(-6) or 10(-8) M) occurred when the peptides were added either simultaneously or 24 h before the stimulatory agent. Similarly, Sertoli cells from 11-day-old rats treated daily with LHRH agonist for 5 days in culture, showed no inhibition of aromatase activity after a 4-h stimulation with FSH or (Bu)2cAMP. FSH dose-response curves (0-300 ng/ml) for aromatase activity were shown to be similar after 5 days of culture with or without 10(-8) M LHRH agonist, indicating that the LHRH did not cause a shift in the sensitivity to FSH. The lack of inhibition was seen in Sertoli cell cultures maintained at 37 or 32 C. The enzyme digestion method used to isolated Sertoli cells was not responsible for the lack of effects of LHRH, since cell cultures prepared without the aid of proteolytic enzymes showed similar FSH stimulation of aromatase activity in the presence or absence of 10(-8) M agonist. Further, there was no evidence of degradation of the LHRH agonist when incubated with Sertoli cell cultures. From these studies, we conclude that 1) granulosa cells and Sertoli cells from immature rats differ in their responses to LHRH, and 2) the immature Sertoli cell is an unlikely target for a direct inhibiting influence of LHRH on spermatogenesis.
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PMID:Differential effects of luteinizing hormone-releasing hormone on follicle-stimulating hormone-dependent responses in rat granulosa cells and Sertoli cells in vitro. 678 Mar 24

FSH is synthesized and secreted by the anterior pituitary gland in multiple molecular forms; the release of these isoforms depends on the endocrine status of the donor at the time of sample collection. In the present study, we analysed the possibility that the FSH charge isoforms may exert differential effects at the target cell. Seven FSH isoform mixes were isolated from pooled anterior pituitary glycoprotein extracts by high resolution chromatofocusing, followed by affinity chromatography, which removed nearly 90% of the LH that co-eluted with the FSH isoforms during chromatofocusing. The isoforms (isoform I, pH >7.10; II, pH range 6.60-6.20; III, pH 5. 47-5.10; IV, pH 5.03-4.60; V, pH 4.76-4.12; VI, pH 4.05-3.82 and VII, pH <3.80) were then tested for their capacity to stimulate cAMP release, androgen aromatization and tissue-type plasminogen activator (tPA) enzyme activity and cytochrome P450 aromatase, tPA and inhibin alpha-subunit mRNA production by rat granulosa cells in culture. cAMP and oestradiol production were determined by RIA, tPA enzyme activity by SDS-PAGE and zymography and all mRNAs by northern blot hybridization analysis and semiquantitative RT-PCR. All isoforms, with the exception of isoform I, stimulated synthesis and release of cAMP, oestrogen and tPA enzyme activity in a dose-dependent manner; the potency of the less acidic isoforms (pH 6. 60-4.60) was greater than that exhibited by the more acidic/sialylated analogs (pH 4.76 to <3.80; potencies II>III>IV>V>VII>VI). A similar trend was observed in terms of cytochrome P450 aromatase and tPA mRNA production. In contrast, when FSH-stimulated production of alpha-inhibin mRNA was analysed, isoforms V-VII were significantly more potent (two- to threefold) than the less acidic/sialylated counterparts (II-IV). In contrast to isoforms II-VII (which behaved as FSH agonists), isoform I (elution pH >7.10) completely blocked P450 aromatase and tPA mRNA expression, without altering that of a constitutively expressed gene (glyceraldehyde-3-phosphate dehydrogenase). These results show for the first time that the naturally occurring human FSH isoforms may exhibit differential or even unique effects at the target cell level.
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PMID:Differential effects of the charge variants of human follicle-stimulating hormone. 1081 Feb 83


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