SEARCH · PubMed Health

Results for “Luteinization”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 901 records · Page 50Linked to original sources

PubMed1981

Thymosin stimulates secretion of luteinizing hormone-releasing factor.

Partially purified thymosin fraction 5 and one of its synthetic peptide components, thymosin beta 4, but not thymosin alpha 1, stimulated secretion of luteinizing hormone--releasing factor from superfused medial basal hypothalami from random cycling female rats. In addition, luteinizing hormone was released from pituitary glands superfused in sequence with hypothalami. No release of luteinizing hormone in response to thymosin was observed from pituitaries superfused alone. These data provide the first evidence of a direct effect of the endocrine thymus on the hypothalamus and suggest a potentially important role for thymic peptides in reproductive function.

Animals↗

PubMed1988

Dose response of luteinized porcine granulosa cells in vitro to prolactin: dependency on pre-exposure to human chorionic gonadotrophin.

This study examined the hypothesis that human chorionic gonadotrophin (hCG) increases prolactin (PRL) stimulation of the utilization of lipoprotein-borne cholesterol by pig luteinized granulosa cells in culture. These cells, which luteinize in culture, were harvested from 6-mm or greater diameter follicles and cultured in the presence of 1% fetal calf serum and 1 microgram/mL insulin for 48 h. On the third day, the media were replaced with fresh serum-free media, with the same dose of insulin, and on the following day (day 4) the media were replaced with serum- and insulin-free media. At this time (day 4) hCG was added to some cultures. On day 5, cells from the group with hCG and cells from the group without hCG were treated with graded doses of ovine PRL (0.1-3.0 micrograms/mL). To a second set of cells, likewise treated, 100 micrograms of porcine low density lipoprotein (LDL) was added. Two days later (day 7) media were sampled and replaced with media alone or media containing hormones and (or) LDL. On day 9 cultures were terminated. In the cells pre-exposed to hCG, PRL (1 microgram/mL) in the presence of LDL increased progesterone production 1.7-fold (p less than 0.01) on day 7 and 2.2-fold (p less than 0.01) on day 9. In the granulosa cells in culture pre-exposed to hCG, the effect of PRL on LDL utilization was dose dependent and saturable at 1 microgram/mL on days 7 and 9. We conclude that brief pretreatment of luteinized pig granulosa cells with hCG results in a dose-dependent PRL-induced utilization of LDL for progesterone synthesis.

Animals↗

PubMed1988

Effect of prolactin and cyclic AMP on 125I-labelled low density lipoprotein uptake and metabolism by luteinized porcine granulosa cells in culture.

The present study examines the effect of prolactin (PRL) and N6-2(1)-O-dibutyryladenosine 3'5'-cyclic monophosphate (cAMP) on low density lipoprotein (LDL) uptake and metabolism by luteinized porcine granulosa cells in culture. Granulosa cells from preovulatory follicles were plated with 1% serum and 1 microgram/mL of insulin for the first 48 h. Following plating (day 3) the cells were cultured in serum-free media with the same dose of insulin. The next day the medium was replaced with serum- and insulin-free medium, and to some cultures 1.23 IU/mL of human chorionic gonadotrophin (hCG) was added. On day 5 the medium was again replaced and graded amounts of PRL (0, 0.03, 0.3, and 3 micrograms/mL) were added. Following 48 h of incubation with PRL, 20 micrograms/mL of 125I-labelled LDL was added to cultures. Surface-bound, internalized, and degraded LDLs were quantitated at 12 h following addition of LDL. To examine the effect of cAMP on LDL metabolism, the cells were exposed for 24 h to cAMP (3mM) on day 6 of culture. PRL had a stimulatory effect on LDL degradation by luteinized granulosa cells. Pre-exposure of cells to hCG augmented the stimulatory effect of PRL. Addition of cAMP also enhanced LDL degradation by luteinized granulosa cells. Both PRL and cAMP increased surface binding of LDL in cells pre-exposed to hCG, but there was no effect on internalization. The increase in cell surface binding of LDL with PRL and cAMP was less than their effect on LDL degradation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Solitary luteinized follicle cyst of pregnancy. Report of a case with cytologic findings.

BACKGROUND: Giant luteinized follicle cyst is a recently recognized cause of ovarian enlargement during pregnancy and the puerperium. Only rare cases of this clinical condition have been reported in the literature, and the cytologic features have not been previously described. CASE: A 34-year-old, pregnant woman presented at 10 weeks' gestation with a large, right ovarian cyst. Clinical management was initially conservative, but four weeks later the patient presented with acute abdominal pain. At laparotomy, the ovarian cyst was aspirated and a cystectomy performed. On cytologic examination, the presence of a luteinized follicle cyst of pregnancy was suggested. Subsequent histologic examination confirmed the diagnosis. CONCLUSION: This case illustrates the clinicopathologic features of a luteinized follicle cyst of pregnancy with special emphasis on the cytologic characteristics. The cytologic features are sufficient to establish the diagnosis in conjunction with the ultrasonographic appearance.

Adult↗

PubMed1990

Place of luteinizing hormone releasing hormone agonists in the treatment of prostatic cancer.

Prolonged administration of a luteinizing hormone releasing hormone agonist causes a transient increase in serum testosterone concentrations, lasting a few days, followed by a long-lasting decrease in the serum testosterone concentrations, luteinizing hormone releasing hormone agonists inducing a chemical castration equivalent to surgical castration. The effect is observed whatever the agonist employed, side-effects being limited to loss of libido, impotence and hot flushes. Moreover, chemical castration is reversible and may be repeated; therefore, this new therapy appears to be of considerable interest in the treatment of prostatic cancer. The indications for luteinizing hormone releasing hormone analogues, however, are limited to metastasized adenocarcinomas which represent the stage of the disease most frequently encountered (about 75% of the cancers treated). They constitute a method of treatment that is only palliative. The use of agonists competes directly with orchidectomy but it is costly and demanding, and it derives its indications from the fact that it is reversible, does not mutilate and is devoid of toxicity.

Gonadotropin-Releasing Hormone↗

PubMed2003

The role of the carotenoids, lutein and zeaxanthin, in protecting against age-related macular degeneration: a review based on controversial evidence.

PURPOSE: A review of the role of the carotenoids, lutein and zeaxanthin, and their function in altering the pathogenesis of age-related macular degeneration (AMD). METHODS: Medline and Embase search. RESULTS: Recent evidence introduces the possibility that lutein and zeaxanthin, carotenoids found in a variety of fruits and vegetables may protect against the common eye disease of macular degeneration. This potential and the lack to slow the progression of macular degeneration, has fueled high public interest in the health benefits of these carotenoids and prompted their inclusion in various supplements. The body of evidence supporting a role in this disease ranges from basic studies in experimental animals to various other clinical and epidemiological studies. Whilst some epidemiological studies suggest a beneficial role for carotenoids in the prevention of AMD, others are found to be unrelated to it. Results of some clinical studies indicate that the risk for AMD is reduced when levels of the carotenoids are elevated in the serum or diet, but this correlation is not observed in other studies. Published data concerning the toxicity of the carotenoids or the optimum dosage of these supplements is lacking. CONCLUSION: An intake of dietary supplied nutrients rich in the carotenoids, lutein and zeaxanthin, appears to be beneficial in protecting retinal tissues, but this is not proven. Until scientifically sound knowledge is available we recommend for patients judged to be at risk for AMD to: alter their diet to more dark green leafy vegetables, wear UV protective lenses and a hat when outdoors. Future investigations on the role of nutrition, light exposure, genetics, and combinations of photodynamic therapy with intravitreal steroid (triamcinolone-acetonide) injections hold potential for future treatment possibilities.

Journal Article↗

PubMed1987

Tissue distribution and hormonal regulation of messenger ribonucleic acid for regulatory and catalytic subunits of adenosine 3',5'-monophosphate-dependent protein kinases during ovarian follicular development and luteinization in the rat.

cDNA probes specific for the regulatory (R) subunits [RII51; (mol wt, 51,000) and RI (mol wt, 49,000)] and a catalytic (C alpha) subunit of cAMP-dependent protein kinases were used to analyze the hormonal regulation, tissue distribution, and content of mRNAs for these kinase subunits in the rat ovary. Filter hybridization assays demonstrated that mRNA specific for RII51 increased in both thecal and granulosa cells of preovulatory (PO) follicles, then declined precipitously (less than 10-fold) in both cell types within 7 h after an ovulatory (10-IU) dose of hCG and remained low in corpora lutea. Dose-response studies showed that doses of FSH greater than 2 micrograms were required to increase RII51 mRNA in granulosa cells of hypophysectomized (H) rats, whereas doses of 0.5-1.0 micrograms were effective in granulosa cells of H estradiol-treated (HE) rats. At all doses (0.5-50 micrograms) of FSH administered, RII51 mRNA was 4 times higher in granulosa cells of HE rats than in H rats. Solution hybridization assays demonstrated that the concentration of RII51 mRNA increased 6-fold from 20 molecules/granulosa cell in H rats to 120 molecules/cell in H rats treated with estradiol and FSH (HEF). Transcription assays using nuclei of granulosa cells demonstrated further that the 5- to 10-fold increases in RII51 mRNA content in estradiol-/FSH-induced granulosa cells was associated with increased transcription of the RII51 gene. In thecal cells of small antral (SA), PO, and luteinizing follicles, changes in the content of mRNA for RI and C alpha kinase subunits showed a pattern similar to that for RII51. However, in granulosa cells, mRNA specific for RI and C alpha was highest in SA follicles, declined in PO follicles, and remained unchanged during luteinization. The content of mRNA for RI (45-70 molecules/cell) and C alpha (10 molecules/cell) also changed less than 2-fold in granulosa cells of H, HE, and HEF rats. In summary, these results indicate that the content of RII51 mRNA is hormonally regulated in both thecal cells and granulosa cells during follicular development and luteinization. Low concentrations of gonadotropins increase RII51 mRNA, whereas an ovulatory dose of hCG causes mRNA for RII51 to decrease rapidly. In granulosa cells, induction of mRNA for RII51, but not that for RI and C alpha is induced by the actions of estradiol and FSH, and involves increased transcription of the RII51 gene.

Animals↗

PubMed1990

Gonadotropin-induced up- and down-regulation of rat ovarian LH receptor message levels during follicular growth, ovulation and luteinization.

Induction of follicular growth by PMSG is associated with increased ovarian LH receptor content, whereas the preovulatory surge of LH decreases LH binding sites, followed by a secondary increase in receptor numbers coincident with corpora lutea formation. Based on the recently reported LH receptor cDNA sequence, we have performed a reverse transcription-polymerase chain reaction to obtain LH receptor cDNA clones and generated a 32P-labeled cRNA probe to examine the dynamic changes in ovarian LH receptor mRNA levels during gonadotropin induction of follicular growth, ovulation and luteinization. Northern blot analysis of ovary RNA revealed hybridization signals of about 7.0, 4.2, 2.5 and 1.8 kb, with no hybridization to nongonadal tissues. PMSG increased the intensity of all four LH receptor messages at 24 h, preceding an increase in LH receptor number, with peak LH receptor mRNA and receptor content observed at 52 h. Treatment with hCG resulted in decreased LH receptor binding and mRNA levels by 6 h after injection, with maximal inhibition (greater than 85%) of message at 12 to 24 h after hCG treatment. Subsequently, LH receptor message levels increased again at 3 days after hCG, concomitant with increased [125I]hCG binding. A further increase in LH receptor content, but not message levels, was observed 5 days after hCG. These results demonstrate that the induction of LH receptors by PMSG is preceded by increased LH receptor mRNA levels. Furthermore, ligand-induced down-regulation of the LH receptor following an ovulatory dose of hCG is associated with decreased LH receptor message content, followed by increases in LH receptor message levels and binding sites during subsequent luteinization. Thus, the up- and down-regulation of ovarian LH receptors during follicle growth, ovulation and luteinization is probably due, at least in part, to changes in receptor message modulation.

Animals↗

PubMed1995

Luteinization in primates is accompanied by loss of a 43-kilodalton adenosine 3',5'-monophosphate response element-binding protein isoform.

Although granulosa cell differentiation and corpus luteum function are both regulated by cAMP, there are development-dependent differences, particularly at the level of gene expression and cell proliferation, between the responses of follicular granulosa cells and luteal cells to trophic hormone stimulation. In this study, we sought to determine whether these differences could be due to changes in the cellular expression of cAMP response element (CRE)-binding protein (CREB). Immunocytochemical analysis of macaque ovaries revealed a development-related alteration in the subcellular distribution of CREB-immunoreactive material. Immunoreactive CREB was present in nuclei of follicular granulosa cells from maturing follicles, whereas after ovulation and luteinization, no CREB-immunoreactive proteins were visualized in luteal cell nuclei. Anti-CREB immunoblotting of granulosa cell extracts from macaque preovulatory follicles as well as extracts of granulosa cells from luteinizing human follicles revealed a 43-kilodalton (kDa) protein, a size typical of native CREB. In contrast, whole cell extracts of monkey corpora lutea collected during the early, mid-, and late luteal phases completely lacked a 43-kDa CREB signal. The absence of 43-kDa CREB isoforms in corpora lutea was confirmed using three different antisera directed against different regions of CREB. Using a human collagenase gene CRE to probe Southwestern blots, a 43-kDa CREB was observed in follicular cell extracts, whereas no CRE-binding activity was found in corpora lutea extracts using this probe. We also sought to determine whether the loss of expression of the 43-kDa CREB isoform may be functionally correlated with the cessation of cellular proliferation that accompanies luteinization. Expression of proliferating cell nuclear antigen (PCNA), an obligatory component of DNA polymerase delta, is essential for proliferation and has been shown by others to be CRE dependent. Immunoblotting of follicle cell and luteal cell extracts with an anti-PCNA monoclonal antibody revealed PCNA expression in granulosa cells and no detectable PCNA expression in corpora lutea. These findings indicate that as follicular granulosa cells progress from the proliferative state to terminally differentiated luteal cells, there is a cessation of expression of a 43-kDa member of the CREB family of transcription factors, and there may be an association between the loss of CREB isoforms and cessation of PCNA expression.

Animals↗

PubMed1999

Pituitary adenylate cyclase-activating polypeptide is an auto/paracrine stimulator of acute progesterone accumulation and subsequent luteinization in cultured periovulatory granulosa/lutein cells.

Recently, we have demonstrated that pituitary adenylate cyclase-activating polypeptide (PACAP) is transiently expressed in steroidogenic ovarian cells during the periovulatory period. This prompted us to establish an in vitro system in which the potential local regulatory role of PACAP during periovulatory progesterone production could be examined. Granulosa/lutein cells from PMSG- and human CG (hCG)-stimulated immature rats were used. The cells were isolated from preovulatory follicles 4-6 h after the hCG injection, at which time the transient ovarian PACAP expression begins in vivo. By immunocytochemistry on intact cells and RIA on cell extracts and culture medium, granulosa/lutein cells were found to accumulate and secrete PACAP during incubation. Furthermore, the cells responded to exogenous PACAP 38 with a rapid (10(-7) M induced a peak value 20-fold higher than controls at 2 h) and dose-dependent accumulation of progesterone. PACAP 38 (5 x 10(-9) M), in combination with an approximately half-maximal dose of hCG (1 ng/ml), showed an additive effect on progesterone accumulation. Immunoneutralization of endogenously released PACAP was performed using the IgG fraction from a specific PACAP antiserum that dose-dependently inhibits the progesterone accumulating effect of exogenous PACAP 38. The acute effects of endogenously released PACAP were studied during 8 h of incubation of granulosa/lutein cells with anti-PACAP IgG (100 microg/ml). A significant reduction in progesterone accumulation was observed after 4, 6, and 8 h [38.7% (P < 0.05), 41.2% (P < 0.02), and 50% (P < 0.002), respectively], compared with nonimmune IgG (100 microg/ml) treated cultures. The long-term effects on luteinization induced by endogenously released PACAP were studied after incubation of the cells with anti-PACAP IgG or nonimmune IgG for 24 h, followed by incubation for 9 days in serum-containing medium. Under these conditions, nonimmune IgG-treated cells assumed a luteal phenotype, accumulating large and stable amounts of progesterone and acquiring hypertrophic cell bodies with numerous lipid droplets and distinct nucleoli in the large nuclei. Anti-PACAP IgG-treated cells displayed morphological and functional signs of impaired luteinization being smaller and more irregular and with progesterone accumulation being significantly lower throughout the incubation period [56.4% (P < 0.02), 69.2% (P < 0.05), 43.8% (P < 0.02), and 52.2% (P < 0.02) at 1, 4, 7, and 10 days, respectively]. Together, these findings support an auto- or paracrine role for PACAP during gonadotropin-induced acute periovulatory progesterone production and subsequent luteinization in granulosa/lutein cells.

Animals↗

PubMed1984

Human preovulatory follicular fluid, luteinized cells of hyperstimulated preovulatory follicles, and corpus luteum contain placental protein 12.

RIA gel filtration, isoelectric focusing; and immunoperoxidase staining were employed to study the occurrence and physicochemical characteristics of placental protein 12 (PP12) in the human ovary, corpus luteum, and preovulatory follicular fluid. Fluid aspirated from 75 follicles from 22 women hyperstimulated for in vitro fertilization contained 6-230 micrograms/liter PP12-like immunoreactive material. The dose-response curves of follicular fluid PP12, amniotic fluid PP12, and purified human placental PP12 were parallel in the PP12 RIA. In gel filtration, follicular fluid PP12 eluted in the same volume as purified PP12. The isoelectric point of follicular fluid PP12 was 4.9 and that of purified placental PP12 4.6-4.7. A positive correlation was found between follicular fluid estradiol and PP12, progesterone and PP12, and follicular fluid volume and PP12 concentrations. By immunoperoxidase staining, PP12 was not detectable in unstimulated ovarian tissue before ovulation. In hyperstimulated preovulatory follicles biopsied in connection with follicle aspiration, PP12 was found in the granulosa cells which were luteinized (n = 3), whereas in those hyperstimulated follicles (n = 5) with no luteinization, no PP12 was found either. PP12 was seen in all corpora lutea (n = 5) from unstimulated menstrual cycles. These results show that the occurrence of PP12 is not limited to the placenta. The correlation between follicular fluid steroid and PP12 levels and the findings by immunoperoxidase staining suggest that PP12 is related to endocrine phenomena of the ovary, possibly to the luteinization process.

Chromatography, Gel↗

PubMed1985

Human chorionic gonadotropin and 8-bromo-adenosine 3',5'-monophosphate stimulate [125I]low density lipoprotein uptake and metabolism by luteinized human granulosa cells in culture.

In nonsteroidogenic cells, cellular cholesterol requirements and sterol availability determine low density lipoprotein (LDL) receptor expression and LDL metabolism. We wished to learn if hCG and cAMP increase LDL metabolism by cultured luteinized human granulosa cells and whether this increase is dependent on enhanced metabolism of cellular cholesterol stores to steroid. Granulosa cells were cultured for 48 h in medium containing 20% human male serum and then for 48 h in serum- and hormone-free medium. The cells then received either fresh medium (no additions) or one of the following treatments: 500 mIU hCG/ml, 1.5 mM 8-bromo-cAMP, 100 micrograms aminoglutethimide (AG)/ml to inhibit cholesterol metabolism to steroid hormones, hCG plus AG, or 8-bromo-cAMP plus AG. After 6-48 h of exposure to tropic agents, specific metabolism of [125I]LDL was determined. hCG and 8-bromo-cAMP significantly increased (P less than 0.05) the amount of [125I]LDL bound (2.2-fold), internalized (2.3-fold), and degraded (2.9-fold) by the luteinized granulosa cells. The apparent Km values for LDL degradation in control and hCG-treated cells were similar (2.0 and 2.6 micrograms/ml, respectively). As little as 10 mIU hCG/ml stimulated LDL metabolism in a time-dependent fashion: a stimulatory effect was detected within 6 h of exposure to hCG and was greater after 24 h. AG attenuated but did not prevent the hCG- or 8-bromo-cAMP-stimulated increase in both LDL uptake and metabolism, although it completely inhibited the steroidogenic response. AG alone had no significant effect on [125I] LDL metabolism. We conclude that hCG and cAMP increase LDL metabolism by luteinized human granulosa cells. These effects are apparently not simply a consequence of enhanced cellular cholesterol metabolism to steroids.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2002

Muscarinic receptors in human luteinized granulosa cells: activation blocks gap junctions and induces the transcription factor early growth response factor-1.

Acetylcholine (ACh) was recently described to be produced by and act on human luteinizing granulosa cells (GCs). Cholinergic agents increase intracellular calcium levels and stimulate GC proliferation via muscarinic receptors. Based on this observation and because endocrine cells of the forming human corpus luteum (CL), which are the in vivo counterparts of GCs, also proliferate in vivo, we hypothesized that ACh may be a factor involved in the regulation of the complex cellular events occurring during ovulation and formation of the CL. We addressed this possibility by investigating ACh/muscarinic receptor-mediated events in GCs. Normally, cultured GCs and their in vivo counterparts are coupled via gap junctions (GJ) consisting of connexin 43. Treatment with carbachol impaired GJ coupling of GCs within seconds, as shown in single cell, whole cell, patch-clamp studies. The cholinergic antagonist atropine and the muscarinic receptor antagonist pirenzepine specifically blocked this effect. Disruption of GJ communication of GCs is probably due to increased phosphorylation of connexin 43 at serine residues, as shown in immunoprecipitation experiments with carbachol-challenged GCs. Ovulation/formation of the CL include reprogramming of luteinizing cells, and in the rat this involves gonadotropin- induced expression of the transcription factor early growth response factor-1 (egr-1). In human GCs we found that carbachol as well as hCG can mimic this effect, as shown by cDNA arrays and semiquantitative RT-PCR. In conclusion, our results obtained in GCs suggest that endogenous, locally produced ACh may contribute to the cellular remodeling of the forming CL via muscarinic receptor/egr-1, thereby affecting proliferation, GJ communication, and regulation of gene expression in luteinizing granulosa cells.

Carbachol↗

PubMed1990

Aromatase cytochrome P450 in rat ovarian granulosa cells before and after luteinization: adenosine 3',5'-monophosphate-dependent and independent regulation. Cloning and sequencing of rat aromatase cDNA and 5' genomic DNA.

The complete nucleotide sequence for rat ovarian aromatase cytochrome P450 (P450arom) has been derived from four cDNA clones isolated from three rat granulosa/luteal cell lambda gt11 cDNA expression libraries. The composite P450arom cDNA extends 1597 basepairs, encodes a protein of 508 amino acids (calculated mol wt = 58,263), and hybridizes to three mRNA transcripts (3.3, 2.6, and 1.9 kilobases in size) in rat ovarian tissues. A 5' genomic fragment was isolated from a rat genomic library and shown to contain exon I and 538 basepairs of 5' flanking sequences, including putative promoter elements. Further, we document that P450arom mRNA and estradiol (E) biosynthesis are regulated by cAMP-dependent mechanisms in granulosa cells of preovulatory (PO) follicles, but are maintained by cAMP-independent mechanisms after LH/hCG-induced luteinization. The transition of the PO granulosa cell to the luteal cell (PO + hCG) phenotype requires 5 h of exposure to hCG in vivo. Once the luteal cell phenotype is programed, P450arom mRNA and E biosynthesis are maintained in the luteinized cells for up to 10 days in a constitutive manner in the absence of hormones or agents that increase intracellular cAMP. Furthermore, when PO + hCG (7 h) follicles were isolated and incubated for 1-3 h with reversible inhibitors of transcription (actinomycin-D) or translation (cycloheximide) before harvesting the granulosa cells, neither morphological nor functional luteinization of granulosa cells in culture was impaired. Thus, rapid cellular and molecular events occur in granulosa cells within 5-7 h after an ovulatory LH/hCG surge that alter the hormonal regulation of the aromatase gene.

Amino Acid Sequence↗

PubMed2002

Novel signaling pathways that control ovarian follicular development, ovulation, and luteinization.

The interactions of peptide and steroid hormone signaling cascades in the ovary are critical for follicular growth, ovulation, and luteinization. Although the pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play key regulatory roles, their actions are also dependent on other peptide signaling pathways, including those stimulated by insulin-like growth factor-1 (IGF-1), transforming growth factor-beta (TGF-beta) family members (e.g., inhibin, activin, growth differentiation factor-9, bone morphogenic proteins), fibroblast growth factor, and Wnts (via Frizzled receptors). Each of these factors is expressed and acts in a cell-specific manner at defined stages of follicular growth. IGF-1, estrogen, and FSH comprise one major regulatory system. The Wnt/Frizzled pathways define other aspects relating to ovarian embryogenesis and possibly ovulation and luteinization. Likewise, the steroid receptors as well as orphan nuclear receptors and their ligands impact ovarian cell function. The importance of these multiple signaling cascades has been documented by targeted deletion of specific genes. For example, mice null for the LH-induced genes progesterone receptor (PR) and cyclo-oxygenase-2 (COX-2) fail to ovulate. Whereas PR appears to regulate the induction of novel proteases, COX-2 appears to regulate cumulus expansion. This review summarizes some new aspects of peptide and steroid hormone signaling in the rodent ovary.

Animals↗

PubMed1978

Androgen aromatization by luteinized bovine granulosa cells in tissue culture.

Luteinized bovine granulosa cells in tissue culture contained an active 19-hydroxylase aromatase enzyme system which converted exogenous androstenedione and testosterone to oestradiol-17beta; no oestrone was detected. In the absence of exogenous androgens, the cells failed to synthesize oestrogens due to a limited capacity to synthesize androgen precursor. Theca-lutein cells, present in those CL which synthesize oestrogens, may provide androgen precursor for aromatization by the granulosa-lutein cells.

Androstenedione↗

PubMed2006

Rapid effects of pesticides on human granulosa-lutein cells.

Following our previous demonstration that p,p'-DDE (dichlorodiphenylchloroethylene), at environmentally relevant concentrations, can rapidly increase intracellular calcium [Ca2+]i concentrations in human granulosa-lutein cells, we examined whether other pesticides, such as Kepone, o,p-DDE and methoxychlor, have similar effects. Cultured human granulosa-lutein cells were loaded with Fura-2 AM, and changes in [Ca2+]i concentrations within small areas of single cells were studied with a dynamic digital Ca2+ imaging system. Kepone, at concentrations of 0.2-2 nmol/ml, consistently increased [Ca2+]i concentrations 2-6 times higher than baseline values within minutes of exposure. Methoxychlor at concentrations of 2.8-280 nmol/ml failed to alter [Ca2+]i levels consistently in cells from 10 patients. However, at 0.28 and 1.4 nmol/ml, increases in [Ca2+]i concentrations could be elicited by methoxychlor. The isomer o,p-DDE at 3 nmol/ml increased [Ca2+]i in granulosa cells of 11/20 patients. Pertussis toxin treatment inhibited the [Ca2+]i increases induced by estradiol, p,p'-DDE, o,p-DDE and methoxychlor, but not by Kepone or progesterone, indicating that Kepone and progesterone may act through an insensitive G protein-coupled receptor. The [Ca2+]i increases induced by Kepone also occurred in Ca2+-free medium, suggesting that [Ca2+]i mobilization occurred from the smooth endoplasmic reticulum. Thapsigargin and cyclopiazonic acid, two inhibitors of the endoplasmic reticulum Ca2+ pump, also stimulated [Ca2+]i increases but did not inhibit the Ca2+ response to all the pesticides. These results demonstrate that pesticides can have a rapid effect on human granulosa-lutein cells, and a nongenomic mechanism of action is suggested.

Calcium↗

PubMed1994

Expression of 17 beta-hydroxysteroid dehydrogenase in the rat ovary during follicular development and luteinization induced with pregnant mare serum gonadotrophin and human chorionic gonadotrophin.

Antibodies against human placental 17 beta-hydroxysteroid dehydrogenase (17-HSD) and 17-HSD cDNA were used to study the expression of the corresponding enzyme in the immature rat ovary during follicular development and luteinization, which were induced by treating the animals with pregnant mare serum gonadotrophin (PMSG) or with PMSG followed by human chorionic gonadotrophin (hCG). Immuno-blot analysis indicated that the M(r) of the 17-HSD expressed in rat granulosa cells was 35,000, as previously shown for the human placental enzyme. In immunohistochemical studies of untreated immature rat ovaries, only the granulosa cells from small antral follicles were stained. One day after PMSG treatment, strong expression of 17-HSD was observed in the granulosa cells of growing Graafian follicles. A marked decrease in enzyme expression was observed in preovulatory follicles on day 2 of PMSG treatment, starting from the basal layers of granulosa cells and progressing toward the luminal cells. No 17-HSD expression was detected in luteinized follicles or corpora lutea 22 h after hCG injection. The stroma and theca cells were negative for 17-HSD staining. In Northern hybridization analyses, two 17-HSD mRNAs were detected (1.4 and 1.7 kb). The strongest expression for both mRNAs was detected after 1 day of PMSG treatment, coinciding with maximal immunostaining of the enzyme protein. Down-regulation of 17-HSD observed by immunohistochemistry was reflected in a similar decrease in mRNA expression and the signals were almost undetectable 22 h after hCG injection. Our data suggest that 17-HSD expression in rat granulosa cells is up-regulated during follicular development and, thereafter, the enzyme expression is down-regulated during luteinization.

17-Hydroxysteroid Dehydrogenases↗