Possible involvement of leukotrienes in human luteal function

The present study was undertaken to assess the ability of human corpora lutea to produce leukotriene B4 (LTB4). The maximum capacity of luteal cells to secrete progesterone was attained on day 4, and both the basal production and the responsiveness to hCG decreased thereafter. In contrast, the production of LTB4 by cultured luteal cells was significantly reduced on day 4, but increased thereafter. The basal concentration of LTB4 produced by luteal cells varied from 75 to 590 pg/105 cells/2 days. LTB4 production appeared to decrease concomitantly with increased-progesterone production in cultured luteal cells. Exposure to hCG decreased significantly LTB4 production by cultured luteal cells on day 4. An inhibitor of the lipoxygenase pathway, nordihydroguaiaretic acid (NDGA), inhibited LTB4 production in a dose-dependent manner. However, NDGA did not affect basal progesterone production by the cultured luteal cells. A significant inverse relationship existed between the accumulation rates of progesterone and LTB4 in the luteal cells. Furthermore, the addition of LTB4 inhibited progesterone production in a dose-dependent manner in both the presence and absence of hCG. In conclusion, LTB4 could be synthesized by human corpora lutea in vitro, and correlated inversely with the secretion rates of progesterone. These data suggest that LTB4 produced locally in the corpus luteum may be an important regulator in human luteal regression.

Download Full-text

Estrogen promotes luteolysis by redistributing prostaglandin F2α receptors within primate luteal cells

Reproduction ◽

10.1530/rep-14-0412 ◽

2015 ◽

Vol 149 (5) ◽

pp. 453-464 ◽

Cited By ~ 7

Author(s):

Soon Ok Kim ◽

Nune Markosyan ◽

Gerald J Pepe ◽

Diane M Duffy

Keyword(s):

Estrogen Receptor ◽

Granulosa Cells ◽

Prostaglandin F2α ◽

Luteal Cell ◽

Corpora Lutea ◽

Dependent Manner ◽

Perinuclear Region ◽

Luteal Cells ◽

Progesterone Production

Prostaglandin F2α (PGF2α) has been proposed as a functional luteolysin in primates. However, administration of PGF2α or prostaglandin synthesis inhibitors in vivo both initiate luteolysis. These contradictory findings may reflect changes in PGF2α receptors (PTGFRs) or responsiveness to PGF2α at a critical point during the life span of the corpus luteum. The current study addressed this question using ovarian cells and tissues from female cynomolgus monkeys and luteinizing granulosa cells from healthy women undergoing follicle aspiration. PTGFRs were present in the cytoplasm of monkey granulosa cells, while PTGFRs were localized in the perinuclear region of large, granulosa-derived monkey luteal cells by mid-late luteal phase. A PTGFR agonist decreased progesterone production in luteal cells obtained at mid-late and late luteal phases, but did not decrease progesterone production by granulosa cells or luteal cells from younger corpora lutea. These findings are consistent with a role for perinuclear PTGFRs in functional luteolysis. This concept was explored using human luteinizing granulosa cells maintained in vitro as a model for luteal cell differentiation. In these cells, PTGFRs relocated from the cytoplasm to the perinuclear area in an estrogen- and estrogen receptor-dependent manner. Similar to our findings with monkey luteal cells, human luteinizing granulosa cells with perinuclear PTGFRs responded to a PTGFR agonist with decreased progesterone production. These data support the concept that PTGFR stimulation promotes functional luteolysis only when PTGFRs are located in the perinuclear region. Estrogen receptor-mediated relocation of PTGFRs within luteal cells may be a necessary step in the initiation of luteolysis in primates.

Download Full-text

ROS-Induced GATA4 and GATA6 Downregulation Inhibits StAR Expression in LPS-Treated Porcine Granulosa-Lutein Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/5432792 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Xiaolu Qu ◽

Leyan Yan ◽

Rihong Guo ◽

Hui Li ◽

Zhendan Shi

Keyword(s):

Molecular Mechanisms ◽

Cell Model ◽

Animal Husbandry ◽

Dependent Manner ◽

Progesterone Production ◽

Progesterone Synthesis ◽

Porcine Granulosa Cell ◽

Underlying Mechanisms ◽

Dose Dependent

LPS is a major endotoxin produced by gram-negative bacteria, and exposure to it commonly occurs in animal husbandry. Previous studies have shown that LPS infection disturbs steroidogenesis, including progesterone production, and subsequently decreases animal reproductive performance. However, little information about the underlying mechanisms is available thus far. In the present study, an in vitro-luteinized porcine granulosa cell model was used to study the underlying molecular mechanisms of LPS treatment. We found that LPS significantly inhibits progesterone production and downregulates the expressions of progesterone synthesis-associated genes (StAR, CYP11A1, and 3β-HSD). Furthermore, the levels of ROS were significantly increased in an LPS dose-dependent manner. Moreover, transcriptional factors GATA4 and GATA6, but not NR5A1, were significantly downregulated. Elimination of LPS-stimulated ROS by melatonin or vitamin C could restore the expressions of GATA4, GATA6, and StAR. In parallel, StAR expression was also inhibited by the knockdown of GATA4 and GATA6. Based on these data, we conclude that LPS impairs StAR expression via the ROS-induced downregulation of GATA4 and GATA6. Collectively, these findings provide new insights into the understanding of reproductive losses in animals suffering from bacterial infection and LPS exposure.

Download Full-text

Corpus luteum and endometrial function in ewes post partum: a study in vivo and in vitro

Reproduction Fertility and Development ◽

10.1071/rd9920077 ◽

1992 ◽

Vol 4 (1) ◽

pp. 77 ◽

Cited By ~ 3

Author(s):

JM Wallace ◽

CJ Ashworth ◽

RP Aitken ◽

MA Cheyne

Keyword(s):

Corpus Luteum ◽

Post Partum ◽

Polyacrylamide Gel Electrophoresis ◽

Uterine Horn ◽

Corpora Lutea ◽

Luteal Function ◽

Progesterone Production ◽

Release Device

Induction of ovulation post partum is associated with a high incidence of prematurely regressing corpora lutea. However, inadequate luteal function is not the sole reason for pregnancy failure, because ewes with normal corpus luteum function and successful fertilization also fail to establish pregnancies. The effects of suckling status and the interval from post partum to rebreeding on corpus luteum and endometrial function were examined in vivo and in vitro. Ewes were weaned early or allowed to lactate, induced to ovulate using a progesterone-impregnated controlled internal drug release device and an intramuscular injection of pregnant mare serum gonadotrophin, and inseminated (intrauterine) at either 21 or 35 days post partum (n = 10 per group). A further 10 standard ewes whose interval from parturition was in excess of 150 days were included for comparative purposes. On Day 10 after insemination the pregnancy rate was determined in four ewes from each of the post-partum groups and five standard ewes. These ewes were then ovariectomized and hysterectomized for studies in vitro. The incidence of premature luteal regression, as assessed by progesterone concentrations in peripheral blood was independent of the suckling stimulus but dependent on stage post partum (21 days post partum, 6 of 19 ewes; 35 days post partum, 0 of 19 ewes; P less than 0.05). Luteal function was normal in all standard ewes. Ovulation rate, corpus luteum weight, corpus luteum progesterone content and basal progesterone production in vitro were significantly less in 21-day than in 35-day post-partum ewes. Pregnancy rates as determined on Day 10 or at term were low in all post-partum groups (7 out of the 38 ewes inseminated) compared with standard ewes (8 of 10). Uterine function was assessed by culturing endometrial tissue from the tip and body of each uterine horn in the presence of [3H]leucine for 30 h at 37 degrees C. Incorporation of radiolabel into non-dialysable proteins synthesized and secreted by the endometrium in vitro was independent of uterine horn location and suckling status but was significantly lower (P less than 0.001) in media from 21-day than from 35-day post-partum ewes. Irrespective of treatment group, incorporation of radiolabel was positively correlated with mean plasma progesterone concentrations on Days 2-10 after insemination and with basal progesterone production in vitro. Secreted proteins were detected by two-dimensional-polyacrylamide-gel electrophoresis and fluorography.(ABSTRACT TRUNCATED AT 400 WORDS)

Download Full-text

Effects of prolactin on steroid production by human luteal cells in vitro

Journal of Endocrinology ◽

10.1677/joe.0.0960499 ◽

1983 ◽

Vol 96 (3) ◽

pp. 499-503 ◽

Cited By ~ 9

Author(s):

G. J. S. Tan ◽

J. S. G. Biggs

Keyword(s):

Menstrual Cycle ◽

Ovarian Function ◽

Chorionic Gonadotrophin ◽

Human Chorionic Gonadotrophin ◽

Corpora Lutea ◽

Short Term ◽

Steroid Production ◽

Luteal Cells ◽

Progesterone Production

The effects of prolactin on steroidogenesis were studied in dispersed luteal cells prepared from human corpora lutea of the menstrual cycle. Prolactin, at concentrations of 0·1–1000 ng/ml, had no effect on progesterone production by luteal cells during short-term incubation (3 h). However, in two out of five corpora lutea, higher concentrations of prolactin (100 and 1000 ng/ml) significantly reduced the oestradiol-17β production induced by human chorionic gonadotrophin (hCG; 10 i.u./ml); lower doses of prolactin had little effect. In the remaining corpora lutea, prolactin failed to affect either basal or hCG-induced production of oestradiol-17β. These results are discussed in relation to the mechanism by which prolactin influences human ovarian function.

Download Full-text

Regulation of steroidogenic function of luteal cells by thrombospondin and insulin in water buffalo (Bubalus bubalis)

Reproduction Fertility and Development ◽

10.1071/rd18188 ◽

2019 ◽

Vol 31 (4) ◽

pp. 751 ◽

Cited By ~ 3

Author(s):

Avishek Paul ◽

Meeti Punetha ◽

Sai Kumar ◽

Arvind Sonwane ◽

Vikrant S. Chouhan ◽

...

Keyword(s):

Caspase 3 ◽

Bubalus Bubalis ◽

Dependent Manner ◽

Luteal Function ◽

Luteal Cells ◽

Progesterone Production ◽

Cluster Of Differentiation ◽

Von Willebrand ◽

Willebrand Factor ◽

Angiogenic Marker

The present study examined the effect of exogenous thrombospondin 1 (TSP1) on the steroidogenic function of luteal cells cultured invitro. Furthermore, the transcriptional interaction of insulin with TSP1 and its receptor, cluster of differentiation 36 (CD36) were also investigated. At the highest dose (500ngmL−1) TSP1 significantly downregulated the expression of the angiogenic marker von Willebrand factor (vWF) and progesterone production in cultured luteal cells. Moreover, the simultaneous upregulation in the expression of caspase 3 by exogenous TSP1 was consistent with a reduction in the number of viable luteal cells as determined by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltertrazolium bromide (MTT) assay after 72h of culture. However, the expression of critical enzymes in the progesterone synthetic pathway was not significantly modulated by treatment with TSP1 in cultured luteal cells. Knocking out of endogenous TSP1 with the clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPRassociated protein9 (Cas9) system improved the viability of luteal cells as well as increasing progesterone production and decreasing caspase 3 activation. Insulin treatment suppressed the expression of TSP1 and CD36 in cultured luteal cells in a dose- and time-dependent manner. To conclude, TSP1 acts as a negative endogenous regulator of angiogenesis that attenuates progesterone production, possibly by reducing the number of luteal cells via apoptosis during luteal regression, whereas insulin as a luteinising signal may have inhibited the thrombospondin system for the efficient development of luteal function.

Download Full-text

Lipoxygenase metabolites of arachidonic acid modulate hematopoiesis

Blood ◽

10.1182/blood.v67.6.1675.1675 ◽

1986 ◽

Vol 67 (6) ◽

pp. 1675-1679 ◽

Cited By ~ 34

Author(s):

DS Snyder ◽

JF Desforges

Keyword(s):

Arachidonic Acid ◽

Mononuclear Cells ◽

Nordihydroguaiaretic Acid ◽

Cell Types ◽

Dependent Manner ◽

Myristate Acetate ◽

Human Erythropoietin ◽

Dose Dependent

Abstract Lipoxygenase (LPO) metabolites of arachidonic acid participate in the activation and/or proliferation of a variety of cell types. In this study, we examined the role of LPO metabolites in controlling myelopoiesis and erythropoiesis in vitro. Monocyte depleted cells (MDC) prepared from human whole blood or whole mononuclear cells from human bone marrow were cultured in methylcellulose in the presence of various growth factors. Conditioned media containing human colony stimulating factors (CSF) or the tumor-promoting phorbol ester, phorbol myristate acetate (PMA), were added to induce myelopoiesis. Semipurified human erythropoietin (EPO) was added along with an endogenous source of burst- promoting activity (BPA) to induce erythropoiesis. The LPO inhibitor BW755C blocked all types of colony formation in a dose-dependent manner, with ID50 of 20 and 5 micrograms/mL for myeloid and erythroid colonies, respectively. MDC depleted of T cells were similarly inhibited by BW755C. Similar results were seen with two other LPO inhibitors, 1-phenyl-3-pyrazolidone and butylated hydroxyanisole. A fourth LPO inhibitor, nordihydroguaiaretic acid, inhibited at higher concentrations. Indomethacin, at concentrations that inhibit cyclooxygenase, had no significant effect, either alone or in combination with the LPO inhibitors. These results suggest that certain LPO products may be important mediators of both CSF- and PMA-induced myelopoiesis, and of BPA/EPO-induced erythropoiesis.

Download Full-text

Assessment of the mechanism by which prolactin stimulates progesterone production by early corpora lutea of pigs

Journal of Endocrinology ◽

10.1677/joe.0.1590201 ◽

1998 ◽

Vol 159 (2) ◽

pp. 201-209 ◽

Cited By ~ 36

Author(s):

RE Ciereszko ◽

BK Petroff ◽

AC Ottobre ◽

Z Guan ◽

BT Stokes ◽

...

Keyword(s):

Inositol Phosphate ◽

Specific Binding ◽

Positive Control ◽

Free Calcium ◽

Corpora Lutea ◽

Pkc Inhibitor ◽

Luteal Cells ◽

Progesterone Production ◽

Progesterone Secretion

Previously, we reported that administration of prolactin (PRL) during the early luteal phase in sows increases plasma progesterone concentrations. In the current study, we searched for the mechanisms by which PRL exerts this luteotrophic effect. The objectives of the study were (1) to examine the effect of PRL and/or low-density lipoproteins (LDL) on progesterone production by porcine luteal cells derived from early corpora lutea, and (2) to assess the ability of PRL to activate phosphoinositide-specific phospholipase C (PI-PLC) and protein kinase C (PKC) in these luteal cells. Ovaries with early corpora lutea (day 1-2 of the oestrous cycle) were obtained from the slaughterhouse. Progesterone production by dispersed luteal cells was measured after treatment with PRL, phorbol 12-myristate 13-acetate or inhibitors of PKC in the presence or absence of LDL. LDL increased progesterone concentration in the incubation medium (304.5 vs 178.6 ng/ml in control, P<0.05). PRL augmented LDL-stimulated progesterone secretion by luteal cells (to 416 ng/ml, P<0.05), but PRL alone did not affect progesterone production (209.6 ng/ml, P>0.05). Staurosporine, a PKC inhibitor, inhibited progesterone secretion stimulated by the combined action of LDL and PRL; however, such inhibition was not demonstrated when cells were treated with the PKC inhibitor, H-7. PKC activation was assessed by measuring the specific association of [H]phorbol dibutyrate (H-PDBu) with luteal cells after treatment with PRL or ionomycin (a positive control). PRL and ionomycin increased H-PDBu-specific binding in early luteal cells by 28+/-5.5% (within 5 min) and 70.2+/-19.3% (within 2 min) over control binding respectively (P<0.05). In addition, PRL did not augment the LDL-stimulated progesterone production in PKC-deficient cells. In contrast with PKC, total inositol phosphate accumulation, as well as intracellular free calcium concentrations, were not affected by PRL in the current study. We conclude that PRL, in the presence of LDL, stimulates progesterone production by early corpora lutea in vitro. Moreover, PRL appears to activate PKC, but not PI-PLC, in these cells. Thus intracellular transduction of the PRL signal may involve activation of PKC that is not dependent on PI-PLC.

Download Full-text

Effects of oestradiol and prolactin on progesterone production by rhesus monkey luteal cells in vitro

Acta Endocrinologica ◽

10.1530/acta.0.1080266 ◽

1985 ◽

Vol 108 (2) ◽

pp. 266-272 ◽

Cited By ~ 7

Author(s):

Richard F. Laherty ◽

Daniel Rotten ◽

May Yamamoto ◽

Robert B. Jaffe

Keyword(s):

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Inhibitory Effect ◽

Corpora Lutea ◽

Experimental Conditions ◽

Luteal Cells ◽

Progesterone Production ◽

Mechanical Disruption ◽

Progesterone Secretion

Abstract. The effects of oestradiol and prolactin (Prl) on progesterone production by dispersed monkey luteal cells were examined. Corpora lutea were recovered from monkeys 5–7 days following ovulation induction during the puerperium. The tissue was dispersed by collagenase and mechanical disruption. The resulting cells were incubated in Dulbecco's modified Eagle's medium, containing the hormones to be tested, for 3 h at 37°C. The medium was removed and assayed for progesterone by RIA. Human luteinizing hormone (hLH) produced a significant, dose-related increase in progesterone secretion that was comparable to that produced by dibutyryl cyclic adenosine monophosphate. Human follicle stimulating hormone (hFSH) had no effect upon progesterone production by the luteal cells. Oestradiol (100–10 000 pg/ml) produced a significant, dose-related decrease in both basal and hLH-stimulated progesterone production. Ovine Prl (oPrl) had neither a stimulatory nor an inhibitory effect upon basal progesterone secretion at doses up to 1000 ng/ml. Further, oPrl did not affect hLH-stimulated progesterone production. We conclude that oestradiol is a potent inhibitor of luteal progesterone secretion in vitro and that Prl does not inhibit progesterone production in the primate corpus luteum under these experimental conditions.

Download Full-text

Dioxin exposure and porcine reproductive hormonal activity

Cadernos de Saúde Pública ◽

10.1590/s0102-311x2002000200010 ◽

2002 ◽

Vol 18 (2) ◽

pp. 453-462 ◽

Cited By ~ 33

Author(s):

Ewa L. Gregoraszczuk

Keyword(s):

Corpora Lutea ◽

Dependent Manner ◽

Luteal Cells ◽

Aryl Hydrocarbon ◽

Preovulatory Follicles ◽

Activity Of Enzymes ◽

Primary Monolayer ◽

Dioxin Exposure

To characterize the action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during both the follicular and luteal phases of the ovarian cycle, the direct effect of TCDD was investigated in vitro using a system of primary monolayer cell culture. Granulosa and theca cells were collected from the preovulatory follicles and cultured as a co-culture, thus resembling follicles in vivo. Luteal cells were isolated from the corpora lutea collected during the midluteal phase. In both cases cells were isolated from the ovaries of animals exhibiting natural estrus cycle. Results of these experiments suggest that TCDD decreases estradiol secretion by follicular cells and progesterone secretion by luteal cells in a dose-dependent manner. It was also shown that TCDD disrupts steroidogenesis through its influence on the activity of enzymes involved in the steroid biosynthesis cascade. In luteal cells, its action is mediated via the aryl hydrocarbon receptor (AhR) and is probably independent of estrogen receptor (ER) stimulation. Endocrine disruptors that interfere with estradiol production in the follicles can act as ovulatory disruptors, and while interfering with progesterone production by luteal cells they can act as abortifacients.

Download Full-text

Conversion of 5(10)-oestrene-3β,17β-diol to 19-nor-4-ene-3-ketosteroids by luteal cells in vitro: possible involvement of the 3β-hydroxysteroid dehydrogenase/isomerase

Journal of Endocrinology ◽

10.1677/joe.0.1290233 ◽

1991 ◽

Vol 129 (2) ◽

pp. 233-243 ◽

Cited By ~ 5

Author(s):

C. M. H. Lee ◽

F. R. Tekpetey ◽

D. T. Armstrong ◽

M. W. Khalil

Keyword(s):

Granulosa Cells ◽

Ovarian Follicle ◽

Cell Types ◽

Hydroxysteroid Dehydrogenase ◽

Corpora Lutea ◽

Dependent Manner ◽

Luteal Cells ◽

Porcine Granulosa Cells ◽

Porcine Luteal Cells

ABSTRACT We have previously suggested that in porcine granulosa cells, a putative intermediate, 5(10)-oestrene-3,17-dione is involved in 4-oestrene-3,17-dione (19-norandrostenedione; 19-norA) and 4-oestren-17β-ol-3-one (19-nortestosterone: 19-norT) formation from C19 aromatizable androgens. In this study, luteal cells prepared from porcine, bovine and rat corpora lutea by centrifugal elutriation were used as a source of 3β-hydroxysteroid dehydrogenase/isomerase in order to investigate the role of this enzyme in the biosynthesis of 19-norsteroids. Small porcine luteal cells made mainly 19-norT and large porcine luteal cells 19-norA from 5(10)-oestrene-3β,17β-diol, the reduced product of the putative intermediate 5(10)-oestrene-3,17-dione. However, neither small nor large cells metabolized androstenedione to 19-norsteroids. Serum and serum plus LH significantly stimulated formation of both 19-norA and 19-norT from 5(10)-oestrene-3β,17β-diol, compared with controls. Inhibitors of the 3β-hydroxysteroid dehydrogenase/isomerase (trilostane and cyanoketone) significantly reduced formation of 19-norT in small porcine luteal cells and 19-norA in large porcine luteal cells, although they were effective at different concentrations in each cell type. In parallel incubations, formation of [4-14C]androstenedione from added [4-14C]dehydroepiandrosterone was also inhibited by cyanoketone in both small and large porcine luteal cells in a dose-dependent manner; however, trilostane (up to 100 μmol/l) did not inhibit androstenedione formation in large porcine luteal cells. In addition, the decrease in progesterone synthesis induced by trilostane and cyanoketone (100 μmol/l each) was accompanied by a parallel accumulation of pregnenolone in both cell types. These results suggest that 3β-hydroxysteroid dehydrogenase/isomerase, or a closely related enzyme, present in small and large porcine luteal cells can convert added 5(10)-3β-hydroxysteroids into 19-nor-4(5)-3-kestosteroids in vitro. In the porcine ovarian follicle, therefore, formation of 19-norA from androstenedione can be envisaged as a two-step enzymatic process: 19-demethylation of androstenedione to produce the putative intermediate 5(10)-oestrene-3,17-dione, and subsequent isomerization to 19-norA. In contrast to granulosa cells, porcine luteal cells synthesized 19-norA or 19-norT only when provided with the appropriate substrate. Unfractionated rat luteal cells also metabolized 5(10)-oestrene-3β,17β-diol to a mixture of 19-norA and 19-norT; conversion was inhibited by trilostane. In addition, small bovine luteal cells synthesized mainly 19-norT and formation was also inhibited by trilostane and cyanoketone. In addition to 19-norA, an unknown metabolite, formed in low amounts by large porcine luteal cells, appears to be related to another steroid which accumulated at high inhibitor concentrations; it may represent 5(10)-oestrene-3,17-dione postulated as a putative intermediate formed during 19-norsteroid biosynthesis. Journal of Endocrinology (1991) 129, 233–243

Download Full-text