scholarly journals Expression of Estrogen Receptor α and β in the Rhesus Monkey Corpus Luteum during the Menstrual Cycle: Regulation by Luteinizing Hormone and Progesterone*

Endocrinology ◽  
2000 ◽  
Vol 141 (5) ◽  
pp. 1711-1717 ◽  
Author(s):  
Diane M. Duffy ◽  
Charles L. Chaffin ◽  
Richard L. Stouffer
Keyword(s):  
Estrogen Receptor ◽  
Menstrual Cycle ◽  
Corpus Luteum ◽  
Messenger Rna ◽  
Luteal Phase ◽  
Estrogen Receptor Α ◽  
Corpora Lutea ◽  
Mrna Levels ◽  
Protein Levels ◽  
Late Luteal Phase

Abstract There are conflicting reports on the presence or absence of estrogen receptor (ER) in the primate corpus luteum, and the discovery of a second type of estrogen receptor, ERβ, adds an additional level of complexity. To reevaluate ER expression in the primate luteal tissue, we used semiquantitative RT-PCR based assays and Western blotting to assess ERα and β messenger RNA (mRNA) and protein levels in corpora lutea (n = 3/stage) obtained from adult female rhesus monkeys at early (days 3–5), mid (days 6–8), mid-late (days 10–12), and late (days 14–16) luteal phase of the natural menstrual cycle. ERα mRNA levels did not vary across the stages of the luteal phase, and ERα protein was not consistently detected in luteal tissues. However, ERβ mRNA and protein levels were detectable in early and mid luteal phases and increased (P < 0.05) to peak levels at mid-late luteal phase before declining by late luteal phase. To determine if ERβ mRNA expression in the corpus luteum is regulated by LH, monkeys received the GnRH antagonist antide either alone or with 3 daily injections of LH to simulate pulsatile LH release. Treatment with antide alone or concomitant LH administration did not alter luteal ERβ mRNA levels. When monkeys also received the 3β-hydroxysteroid dehydrogenase inhibitor trilostane to reduce luteal progesterone production, luteal ERβ mRNA levels were 3-fold higher (P < 0.05) than in monkeys receiving antide + LH only. Replacement of progestin activity with R5020 reduced luteal ERβ mRNA levels to those seen in animals receiving antide + LH. Thus, there is dynamic ERβ expression in the primate corpus luteum during the menstrual cycle, consistent with a role for estrogen in the regulation of primate luteal function and life span via a receptor (ERβ)-mediated pathway. Increased ERβ expression in the progestin-depleted corpus luteum during LH exposure suggests that the relative progestin deprivation experienced by the corpus luteum between LH pulses may enhance luteal sensitivity to estrogens during the late luteal phase of the menstrual cycle.

CONCENTRATION OF PROSTAGLANDIN F2α AND STEROIDS IN THE HUMAN CORPUS LUTEUM

1977 ◽  
Vol 73 (1) ◽  
pp. 115-122 ◽  
Author(s):  
I. A. SWANSTON ◽  
K. P. McNATTY ◽  
D. T. BAIRD
Keyword(s):  
Menstrual Cycle ◽  
Corpus Luteum ◽  
Luteal Phase ◽  
Prostaglandin F2α ◽  
Corpora Lutea ◽  
Progesterone Concentration ◽  
Late Luteal Phase ◽  
Prostaglandin F ◽  
Human Corpus Luteum

SUMMARY The concentration of prostaglandin F2α (PGF2α), progesterone, pregnenolone, oestradiol-17β, oestrone, androstenedione and testosterone was measured in corpora lutea obtained from 40 women at various stages of the menstrual cycle. The concentration of PGF2α was significantly higher in corpora lutea immediately after ovulation (26·7 ± 3·9 (s.e.m.) ng/g, P < 0·005) and in corpora albicantia (16·3 ± 3·3 ng/g, P < 0·005) than at any other time during the luteal phase. There was no correlation between the concentration of PGF2α and that of any steroid. The progesterone concentration was highest in corpora lutea just after ovulation (24·9 ± 6·7 μg/g) and in early luteal groups (25·7 ± 6·8 μg/g) but declined significantly (P < 0·05) to its lowest level in corpora albicantia (1·82 ± 0·66 μg/g). The concentration of oestradiol-17β in the corpus luteum and luteal weight were significantly greater during the mid-luteal phase than at any other stage (concentration 282 ± 43 ng/g, P < 0·05; weight 1·86 ± 0·18 g, P < 0·005). The results indicate that regression of the human corpus luteum is not caused by a rise in the ovarian concentration of PGF2α in the late luteal phase of the cycle.

scholarly journals Administration of vascular endothelial growth factor Trap during the ‘post-angiogenic’ period of the luteal phase causes rapid functional luteolysis and selective endothelial cell death in the marmoset

Reproduction ◽  
2006 ◽  
Vol 132 (4) ◽  
pp. 589-600 ◽  
Author(s):  
Hamish M Fraser ◽  
Helen Wilson ◽  
Christine Wulff ◽  
John S Rudge ◽  
Stanley J Wiegand
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Corpus Luteum ◽  
Luteal Phase ◽  
Caspase 3 ◽  
Corpora Lutea ◽  
Vascular Endothelial ◽  
Late Luteal Phase ◽  
Endothelial Growth Factor ◽  
Vegf Trap

The intense angiogenesis characteristic of early corpus luteum development is dependent upon vascular endothelial growth factor (VEGF) as inhibitors of VEGF administered at the peri-ovulatory period suppress endothelial cell proliferation and progesterone secretion. We now report that administration of VEGF Trap, a soluble decoy receptor-based inhibitor, at the mid- or the late luteal phase in the marmoset results in a rapid decline in plasma progesterone. Since vascularisation of the corpus luteum is largely complete by the mid-luteal phase, it suggested that this functional luteolysis involved mechanisms other than inhibition of angiogenesis. A second experiment investigated the role of VEGF in maintaining the integrity of the luteal vasculature and hormone-producing cells. VEGF Trap was administered to marmosets in the mid-luteal phase and ovaries were obtained 1, 2, 4 or 8 days later for localisation of activated caspase-3 staining in the corpus luteum and compared with those obtained 2, 4 and 8 days after administration of control protein. The number of cells with activated caspase-3 staining was significantly increased after administration of VEGF Trap. Dual staining of activated caspase-3 with the endothelial cell marker CD31 showed that at 1 day post-treatment, more than 90% caspase-3-stained cells were vascular endothelium, prior to detection of an increasing incidence in death of hormone-producing cells on days 2 and 4. Staining with CD31 showed that the endothelial cell area was decreased after treatment. By 8 days after treatment, corpora lutea had regressed to varying degrees, while all control corpora lutea remained healthy. These results show that VEGF inhibition in the mid- or the late luteal phase induces functional luteolysis in the marmoset that is associated with premature and selective death of endothelial cells.

scholarly journals Hormonal regulation of connexin-43 in baboon corpora lutea

1998 ◽  
Vol 157 (3) ◽  
pp. 405-414 ◽  
Author(s):  
FS Khan-Dawood ◽  
J Yang ◽  
MY Dawood
Keyword(s):  
Corpus Luteum ◽  
Hormonal Regulation ◽  
Luteal Phase ◽  
Connexin 43 ◽  
Clomiphene Citrate ◽  
Corpora Lutea ◽  
Lh Surge ◽  
Phosphorylated Protein ◽  
Late Luteal Phase ◽  
Cell Cell

The synthesis and secretion of progesterone in the corpus luteum are regulated by both endocrine and paracrine/ autocrine factors which affect the steroidogenic cells. Evidence suggests that these cells communicate via cell-cell junctional proteins, the connexins. Previously we have shown that connexin-43 is expressed in both human and baboon (Papio hamadryus anubis) corpora lutea, with differential expression throughout luteal development, but is not detectable in corpora albicantia. We have examined the effect of human chorionic gonadotropin (hCG), oxytocin, clomiphene citrate and the anti-progesterone onapristone on expression of connexin-43 protein in the early luteal phase 1-5 days after the mid-cycle luteinizing hormone (LH) surge (LH+ 1-5 days), the mid-luteal phase 6-10 days after the LH surge (LH+ 6-10 days), and the late luteal phase 11-15 days after the LH surge (LH+ 11-15 days) in corpora lutea obtained from normal adult cycling females. Connexin-43 was localized by immunohistochemistry in cultured cells from all the three stages. Western blot analysis of the treated cells indicated the presence of two bands at 43 and 45 kDa. The band at 45 kDa was found to be phosphorylated connexin-43, indicating the presence of functional gap junctions. hCG (10 IU/ml) stimulated the expression of connexin-43 throughout luteal development; however, maximum expression occurred in the early luteal phase with a significantly greater expression of the non-phosphorylated protein. In contrast, in the mid-luteal phase, the expression of the phosphorylated protein was predominant. Oxytocin (200 mU/ml) also stimulated connexin-43 expression throughout luteal development with similar effects on the phosphorylated and non-phosphorylated protein in the early and mid-luteal phase; however, compared with hCG, oxytocin had a greater effect on mid-luteal phase connexin-43 expression. In the presence of both hCG and oxytocin, the expression of connexin-43 was significantly higher than the control only in the late luteal phase. Both clomiphene citrate and onapristone suppressed connexin-43 expression, and concomitant addition of hCG did not counteract their effect. In the context of our previous studies, it is concluded that, together with LH/hCG and the steroid hormones, oxytocin is involved in cell-cell contact-dependent communication in the corpus luteum.

scholarly journals Effects of Castration and Chronic Steroid Treatments on Hypothalamic Gonadotropin-Releasing Hormone Content and Pituitary Gonadotropins in Male Wild-Type and Estrogen Receptor-α Knockout Mice

Endocrinology ◽  
1998 ◽  
Vol 139 (10) ◽  
pp. 4092-4101 ◽  
Author(s):  
Jonathan Lindzey ◽  
William C. Wetsel ◽  
John F. Couse ◽  
Tammy Stoker ◽  
Ralph Cooper ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Replacement Therapy ◽  
Signaling Pathways ◽  
Messenger Rna ◽  
Estrogen Receptor Α ◽  
Mrna Levels ◽  
Wild Type ◽  
Feedback Effects ◽  
Serum Lh ◽  
Circulating Levels

Abstract Testicular androgens are integral components of the hormonal feedback loops that regulate circulating levels of LH and FSH. The sites of feedback include hypothalamic areas regulating GnRH neurons and pituitary gonadotropes. To better define the roles of androgen receptor (AR), estrogen receptor-α (ERα), and estrogen receptor-β (ERβ) in mediating feedback effects of sex steroids on reproductive neuroendocrine function, we have determined the effects of castration and steroid replacement therapy on hypothalamic GnRH content, pituitary LHβ and FSHβ messenger RNA (mRNA) levels, and serum gonadotropins in male wild-type (WT) and estrogen receptor-α knockout (ERKO) mice. Hypothalami from intact WT and ERKO males contained similar amounts of GnRH, whereas castration significantly reduced GnRH contents in both genotypes. Replacement therapy with estradiol (E2), testosterone (T), or dihydrotestosterone (DHT) restored hypothalamic GnRH content in castrated (CAST) WT mice; only the androgens were effective in CAST ERKOs. Analyses of pituitary function revealed that LHβ mRNA and serum LH levels in intact ERKOs were 2-fold higher than those in intact WT males. Castration increased levels of LHβ mRNA (1.5- to 2-fold) and serum LH (4- to 5-fold) in both genotypes. Both E2 and T treatments significantly suppressed LHβ mRNA and serum LH levels in CAST WT males. However, E2 was completely ineffective, and T was only partially effective in suppressing these two indexes in the CAST ERKO males. DHT treatments stimulated a 50% increase in LHβ mRNA and serum LH levels in WT males, whereas serum LH was significantly suppressed in DHT-treated ERKO males. Although the pituitaries from intact ERKO males contained similar amounts of FSHβ mRNA, serum FSH levels were 20% higher than those in the intact WT males. Castration increased FSHβ mRNA levels only in WT males, but significantly increased serum FSH levels in both genotypes. Both E2 and T treatments significantly suppressed serum FSH in CAST WT males, whereas only E2 suppressed FSHβ mRNA. DHT treatments of CAST WT mice stimulated a small increase in serum FSH, but failed to alter FSHβ mRNA levels. None of the steroid treatments exerted any significant effect on FSHβ mRNA or serum FSH levels in CAST ERKOs. These data suggest that hypothalamic GnRH contents can be maintained solely through AR signaling pathways. However, normal regulation of gonadotrope function requires aromatization of T and activation of ERα signaling pathways in the gonadotrope. In addition, serum FSH levels in male ERKOs appear to be regulated largely by nonsteroidal testicular factors such as inhibin. Finally, these data suggest that hypothalamic ERβ may not be involved in mediating the negative feedback effects of T on serum LH and FSH in male mice.

Specific binding sites for gonadotrophin-releasing hormone, LH/chorionic gonadotrophin, low-density lipoprotein, prolactin and FSH in homogenates of human corpus luteum. II: Concentrations throughout the luteal phase of the menstrual cycle and early pregnancy

1987 ◽  
Vol 113 (2) ◽  
pp. 317-327 ◽  
Author(s):  
T. A. Bramley ◽  
D. Stirling ◽  
I. A. Swanston ◽  
G. S. Menzies ◽  
A. S. McNeilly ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Corpus Luteum ◽  
Gnrh Agonist ◽  
Luteal Phase ◽  
Specific Binding ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Corpora Lutea ◽  
Agonist Binding ◽  
Gonadotrophin Releasing Hormone

ABSTRACT Corpora lutea were obtained from 52 women undergoing laparotomy during the luteal phase of the menstrual cycle. In addition, stromal, thecal and granulosa cell preparations were obtained from seven women undergoing ovariectomy during the late follicular–preovulatory phase of the cycle. The specific binding of a 125I-labelled gonadotrophin-releasing hormone (GnRH) agonist [d-Ser(But)6] GnRH(1–9)-ethylamide (buserelin) and of human chorionic gonadotrophin (hCG), human FSH (hFSH), human prolactin (hPRL) and human low-density lipoprotein (hLDL) to tissue homogenates was measured under optimal conditions. Bound LH/hCG was estimated by elution with acid-citrate buffer, followed by radioimmunoassay of released hormone. Binding of GnRH agonist, though variable, was highest in mid-luteal corpus luteum and high binding was also present in three out of four corpora lutea of pregnancy. Binding of LH/hCG increased significantly with luteinization, reaching maximal levels in the mid-luteal phase before falling significantly. Occupancy of LH receptors by bound LH was relatively constant throughout the luteal phase (10·7–35·3%), but occupancy increased to >90% in corpora lutea from early pregnancy. Binding of hFSH was variable, with only five out of 50 corpora lutea having binding greater than 10 pg/μg DNA. Similarly, hPRL binding varied markedly with only six out of 44 having binding greater than 50 pg/μg DNA. Binding of LDL was highest in the early- to mid-luteal phases of the cycle. In corpora lutea from all stages of the menstrual cycle (excluding corpora albicantia), GnRH agonist binding was highly correlated with the levels of unoccupied and occupied LH receptors (P < 0·001; n = 49 and n = 48 respectively) and with LDL receptors (P< 0·002; n = 49). Binding of GnRH agonist was also correlated with PRL binding (P<0·05; n = 21) but not with FSH receptors (P>0·4; n = 25). In addition, LDL binding was associated with PRL (P< 0·005; n = 21) and FSH receptors (P<0·05; n = 25) and with endogenously bound LH (P<0·03; n = 48), but not with unoccupied LH receptors (P = 0·8; n = 49). Moreover, in corpora lutea from the mid-luteal phase, there was a strong association between GnRH agonist binding and LDL receptors (P<0·02; n = 23). The correlations between GnRH agonist binding and a number of important indices of luteal function suggest a physiological role for GnRH-like factors in the human corpus luteum. J. Endocr. (1987) 113, 317–327

scholarly journals PARP7 and Mono-ADP-Ribosylation Negatively Regulate Estrogen Receptor α Signaling in Human Breast Cancer Cells

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 623
Author(s):  
Marit Rasmussen ◽  
Susanna Tan ◽  
Venkata S. Somisetty ◽  
David Hutin ◽  
Ninni Elise Olafsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Protein Modification ◽  
Target Genes ◽  
Estrogen Receptor Α ◽  
Transactivation Domain ◽  
Adp Ribosylation ◽  
Protein Levels ◽  
17Β Estradiol ◽  
Mcf 7

ADP-ribosylation is a post-translational protein modification catalyzed by a family of proteins known as poly-ADP-ribose polymerases. PARP7 (TIPARP; ARTD14) is a mono-ADP-ribosyltransferase involved in several cellular processes, including responses to hypoxia, innate immunity and regulation of nuclear receptors. Since previous studies suggested that PARP7 was regulated by 17β-estradiol, we investigated whether PARP7 regulates estrogen receptor α signaling. We confirmed the 17β-estradiol-dependent increases of PARP7 mRNA and protein levels in MCF-7 cells, and observed recruitment of estrogen receptor α to the promoter of PARP7. Overexpression of PARP7 decreased ligand-dependent estrogen receptor α signaling, while treatment of PARP7 knockout MCF-7 cells with 17β-estradiol resulted in increased expression of and recruitment to estrogen receptor α target genes, in addition to increased proliferation. Co-immunoprecipitation assays revealed that PARP7 mono-ADP-ribosylated estrogen receptor α, and mass spectrometry mapped the modified peptides to the receptor’s ligand-independent transactivation domain. Co-immunoprecipitation with truncated estrogen receptor α variants identified that the hinge region of the receptor is required for PARP7-dependent mono-ADP-ribosylation. These results imply that PARP7-mediated mono-ADP-ribosylation may play an important role in estrogen receptor positive breast cancer.

STIMULATION BY HUMAN CHORIONIC GONADOTROPHIN OF OESTRADIOL PRODUCTION BY DISPERSED CELLS FROM HUMAN CORPUS LUTEUM: COMPARISON WITH PROGESTERONE PRODUCTION; UTILIZATION OF EXOGENOUS TESTOSTERONE

1981 ◽  
Vol 91 (2) ◽  
pp. 197-203 ◽  
Author(s):  
M. C. RICHARDSON ◽  
G. M. MASSON
Keyword(s):  
Luteal Phase ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Cell Suspensions ◽  
Corpora Lutea ◽  
Progesterone Production ◽  
Late Luteal Phase ◽  
Oestradiol Production ◽  
Dispersed Cells

Cell suspensions were prepared from tissue samples of human corpora lutea obtained during the mid- and late-luteal phase of the menstrual cycle. Both oestradiol and progesterone production by dispersed cells were stimulated by similar concentrations of human chorionic gonadotrophin (hCG). As the degree of stimulation of production by hCG was greater for progesterone than for oestradiol (five- to tenfold compared with two- to threefold higher than basal production), the ratio of progesterone to oestradiol produced varied according to the level of trophic stimulation. A comparison of cell suspensions prepared from mid- and late-luteal phase corpora lutea, exposed to the same concentration of hCG (10 i.u./ml) in vitro, did not reveal a shift to oestradiol production in the late-luteal phase. Provision of additional testosterone during incubation raised the level of oestradiol production by dispersed luteal cells. At an optimum concentration of testosterone (1 μmol/l), oestradiol synthesis was not raised further in the presence of hCG or N6, O2-dibutyryl cyclic AMP, suggesting a lack of induction or activation of the aromatase system by gonadotrophin in short-term cultures. Basal and stimulated levels of progesterone production were not significantly impaired in the presence of testosterone.

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