scholarly journals Luteinizing Hormone Regulation of Inter-Organelle Communication and Fate of the Corpus Luteum

2021 ◽  
Vol 22 (18) ◽  
pp. 9972
Author(s):  
Emilia Przygrodzka ◽  
Michele R. Plewes ◽  
John S. Davis

The corpus luteum is an endocrine gland that synthesizes the steroid hormone progesterone. luteinizing hormone (LH) is a key luteotropic hormone that stimulates ovulation, luteal development, progesterone biosynthesis, and maintenance of the corpus luteum. Luteotropic and luteolytic factors precisely regulate luteal structure and function; yet, despite recent scientific progress within the past few years, the exact mechanisms remain largely unknown. In the present review, we summarize the recent progress towards understanding cellular changes induced by LH in steroidogenic luteal cells. Herein, we will focus on the effects of LH on inter-organelle communication and steroid biosynthesis, and how LH regulates key protein kinases (i.e., AMPK and MTOR) responsible for controlling steroidogenesis and autophagy in luteal cells.

2016 ◽  
Vol 62 (5) ◽  
pp. 49
Author(s):  
Magdalena Julia Szymańska ◽  
Agnieszka Blitek

Background. Prostacyclin (PGI2) of luteal origin is involved in the control of corpus luteum (CL) development and function in cattle. PGI2 may regulate the process of angiogenesis and may stimulate progesterone (P4) secretion by luteal cells via its specific receptors, PTGIR. In contrast to cattle, the role of PGI2 in the pig CL has not yet been described.Aim. The present study aimed to investigate the effect of PGI2 on 1) P4 secretion by luteal cells, and 2) the expression of angiogenesis-related genes in endothelial cells of the porcine CL.Methods. CL collected from gilts on day 5-7 of the estrous cycle were used for enzymatic isolation of luteal (Experiment 1) and endothelial (Experiment 2) cells. In Exp. 1, cultured luteal cells were incubated with increasing (0, 0.01, 0.1, 1, 5 µM) doses of PGI2 analogues: iloprost (ILO) and carbaprostacyclin (cPGI2) for 8 h. To determine the effective doses of PGI2 analogues, P4 concentration in culture medium was examined by RIA. Thereafter, luteal cells were treated with ILO and cPGI2 at the concentration of 1 and 5 µM in the presence or absence of PTGIR antagonist (CAY10441). After 8 h of incubation the medium was collected for P4 determination. In Exp. 2, isolated endothelial cells were treated for 24 h with ILO and cPGI2 at doses of 1 and 5 µM. Then, cells were collected for analysis of Ang-1 and -2 mRNA expression using qPCR.Results. Both, ILO and cPGI2 affected P4 secretion by luteal cells. Elevated levels of P4 were observed in medium after treatment of luteal cells with 1 µM of ILO and 0.1, 1 and 5 µM of cPGI2 compared with control values (p<0.05). The addition of CAY10441 inhibited the stimulatory effect of ILO on P4 secretion, while did not change P4 production by luteal cells incubated with cPGI2. Moreover, PGI2 analogues differentially affected (p<0.05) the expression of proangiogenic factors. ILO stimulated Ang-2, whereas cPGI2 positively affected Ang-1 mRNA expression in endothelial cells at concentrations of 1 µM and 5 µM, respectively.Conclusion. PGI2 affects P4 secretion during luteal phase of the estrous cycle and may regulate the process of angiogenesis in the porcine CL.


Reproduction ◽  
2006 ◽  
Vol 131 (1) ◽  
pp. 103-111 ◽  
Author(s):  
Alicia A Goyeneche ◽  
Jacquelyn M Harmon ◽  
Carlos M Telleria

The corpus luteum is a transient endocrine gland specializing in the production of progesterone. The regression of the corpus luteum involves an abrupt decline in its capacity for producing progesterone followed by its structural involution, which is associated with apoptosis of the luteal cells. An in vitro experimental approach is needed to study the molecular mechanisms underlying hormonal regulation of luteal cell death under defined experimental conditions. In this study, we investigated simian virus-40-transformed luteal cells to determine whether they can be driven to apoptosis and, if so, to define the intracellular pathway involved. Luteal cells were cultured in the presence or absence of fetal bovine serum for 24 or 48 h. Under serum starvation conditions, the luteal cells underwent growth arrest accompanied by cell death as evaluated by dye exclusion, and confirmed by two-color fluorescence cell viability/cytotoxicity assay. We next studied whether serum starvation-induced death of luteal cells occurred by apoptosis. Morphologic features of apoptosis were observed in cells stained with hematoxylin after being subjected to serum starvation for 48 h. The apoptotic nature was further confirmed by in situ 3′-end labeling and fragmentation of genomic DNA. Apoptosis of serum-deprived luteal cells was dependent upon caspase activation. Serum starvation induced cleavage of poly (ADP-ribose) polymerase (PARP), suggesting that caspase-3 had been activated under the stress of withdrawal of growth factors. This was confirmed by cleavage of full-length procaspase-3. Finally, the fact that serum starvation promoted the cleavage of full-length procaspase-9 and the decrease in the expression of endogenous Bid, a BH-3-only proapoptotic protein of the Bcl-2 family, indicates that the intrinsic (i.e., mitochondrial) pathway of apoptosis was activated. In summary, we have characterized an in vitro experimental model of luteal cell death that can be utilized to evaluate the role of hormones in apoptosis of luteal cells under defined culture conditions, and to study the mechanism of luteal regression.


1997 ◽  
Vol 9 (6) ◽  
pp. 651 ◽  
Author(s):  
R. P. Del Vecchio ◽  
W. D. Sutherland

This experiment examined production of prostaglandin (PG) F2α , PGE2 and progesterone by bovine luteal cells incubated with or without the accessory cells and treated with recombinant bovine interleukin-1β (10 ng), indomethacin (5 µg) or luteinizing hormone (50 ng). During pretreatment, progesterone production was similar in the luteal and luteal plus accessory cells, being greater in either of these than in accessory cells; PGF2α was greatest in luteal plus accessory, intermediate in accessory and lowest in the luteal cells; PGE2 was similar among all cell arrangements. Luteinizing hormone or luteinizing hormone plus indomethacin stimulated progesterone in the luteal and luteal plus accessory cells, this being similar in these two cell arrangements. Interleukin-1β stimulated PGF2α in luteal and luteal plus accessory cells, and tended to elevate PGF2α in accessory cells. Interleukin-1β stimulated PGE2 in all cell arrangements. Indomethacin inhibited the interleukin-1b-stimulated PGF2α and PGE2 release. Indomethacin or indomethacin plus luteinizing hormone inhibited basal PGE2 in luteal and luteal plus accessory cells. These data suggest that progesterone production is not inßuenced by the presence of accessory cells of the corpus luteum, that accessory and luteal cells produce appreciable amounts of PG, and that recombinant bovine interleukin-1b stimulates PGE2 and PGF2α in the luteal and accessory cells.


Author(s):  
R. K. Nayak

The structure and function of the corpus luteum has been studied intensively, yet many of the factors and events in formation, maintenance, function and regression of this endocrine gland remain unclear. Christensen and Gillim reviewed the literature dealing with steroid-secreting cells including lutein cells. They clearly documented the role of smooth endoplasmic reticulum in steroid biosynthesis. The fine structure of the corpus luteum has been described in a variety of animals including rat, mouse, hamster, guinea pig, rabbit, pig, cow, sheep, deer, dog, racoon, mink, badger, lemur, armadillo and man. Recently, Enders reviewed in detail the results obtained on the cytology of corpus luteum granulosa lutein cells of early pregnancy.Novoa has recently attempted to correlate some reproductive phenomena in Camelidae with those of other domestic animals. Since the literature is essentially devoid of information on electron microscopy of the camel corpus luteum and since fresh camel corpus luteum specimens were obtained in excellent condition, a critical study was undertaken to provide definitive information on the structure and function of the corpus luteum during early stages of pregnancy and after parturition in the one-humped camel, Camelus dromedarius.


Reproduction ◽  
2016 ◽  
Vol 151 (3) ◽  
pp. 187-202 ◽  
Author(s):  
JeHoon Lee ◽  
Sakhila K Banu ◽  
John A McCracken ◽  
Joe A Arosh

The corpus luteum (CL) is a transient endocrine gland. Functional and structural demise of the CL allows a new estrous cycle. On the other hand, survival of CL and its secretion of progesterone are required for the establishment of pregnancy. Survival or apoptosis of the luteal cells is precisely controlled by interactions between survival and apoptosis pathways. Regulation of these cell signaling components during natural luteolysis and establishment of pregnancy is largely unknown in ruminants. The objective of the present study was to determine the regulation of survival and apoptosis signaling protein machinery in the CL on days 12, 14, and 16 of the estrous cycle and pregnancy in sheep. Results indicate that: i) expressions of p-ERK1/2, p-AKT, β-catenin, NFκB -p65, -p50, -p52, p-Src, p-β -arrestin, p-GSK3β, X-linked inhibitor of apoptosis protein (XIAP), and p-CREB proteins are suppressed during natural luteolysis; in contrast, their expressions are sustained or increased during establishment of pregnancy; ii) expressions of cleaved caspase-3, apoptosis inducing factor (AIF), c-Fos, c-Jun, and EGR-1 proteins are increased during natural luteolysis; in contrast, their expressions are decreased during establishment of pregnancy; and iii) expressions of Bcl-2, Bcl-XL, Bad, and Bax proteins are not modulated during natural luteolysis while expressions of Bcl2 and Bcl-XL proteins are increased during establishment of pregnancy in sheep. These proteomic changes are evident in both large and small luteal cells. These results together indicate that regression of the CL during natural luteolysis or survival of the CL during establishment of pregnancy is precisely controlled by distinct programmed suppression or activation of intraluteal cell survival and apoptosis pathways in sheep/ruminants.


1999 ◽  
Vol 61 (4) ◽  
pp. 921-926 ◽  
Author(s):  
J.A. Quintal-Franco ◽  
F.N. Kojima ◽  
E.J. Melvin ◽  
B.R. Lindsey ◽  
E. Zanella ◽  
...  

2008 ◽  
Vol 52 (No. 9) ◽  
pp. 405-412 ◽  
Author(s):  
R. Rekawiecki ◽  
J. Kotwica

In bovine luteal cells, progesterone can directly affect its own synthesis by increasing the activity of 3β-HSD. The effect of progesterone on its own secretion coincides with increased expression of the genes for 3β-HSD, StAR, and cytochrome P450scc. Therefore, progesterone regulates its own synthesis by affecting the activity of the enzymes that take part in luteal steroidogenesis, and also by affecting the expression of the genes for these enzymes. The aims of this study were: (a) to determine whether progesterone affects the expression of the gene for its own receptor, thereby affecting its own synthesis; and (b) to determine whether oxytocin and noradrenaline affect the expression of the genes for the oxytocin receptor (OT-R), the progesterone receptor (P4-R), and the β<sub>2</sub> receptor (β<sub>2</sub>-R), thereby regulating luteal steroidogenesis. Two populations of luteal cells were used in the present study: from 6<sup>th</sup>–10<sup>th</sup> and 11<sup>th</sup>–16<sup>th</sup> days of the estrous cycle, which were isolated from <i>corpus luteum</i> (CL) from slaughtered cows. The luteal cells were treated for six hours with one of the following hormones: luteinizing hormone (LH; 100 ng/ml); progesterone (P<sub>4</sub>; 10<sup>–5</sup>M); progesterone antagonist (aP<sub>4</sub>; 10<sup>–5</sup>M); noradrenaline (NA; 10<sup>–5M</sup>); or actinomycin D (ActD; 500 ng/ml). After treatment, the medium was collected for the determination of progesterone concentration. With LH, the P<sub>4</sub> concentration in the medium increased with both 6<sup>th</sup>–10<sup><sup>th</sup> and 11<sup>th</sup>–16<sup>th</sup> days. None of the other treatments affected the progesterone concentration of the medium. The level of expression of the genes for OT-R, P<sub>4</sub>-R and β<sub>2</sub>-R were determined. Total RNA was extracted from cells, treated with DNase, and subjected to reverse transcription. Treatment with luteinizing hormone was the only treatment that increased the level of expression of the gene for P<sub>4</sub>-R in both 6<sup>th</sup>–10<sup>th</sup> and 11<sup>th</sup>–16<sup>th</sup> days of the estrous cycle. Both treatment with luteinizing hormone and treatment with progesterone increased the level of expression of the gene for OT-R in 6<sup>th</sup>–10<sup>th</sup> days. The basal level of expression of the gene for OT-R was higher in 6<sup>th</sup>–10<sup>th</sup> days than in 11<sup>th</sup>–16<sup>th</sup> days. This suggests that there is positive feedback between progesterone and oxytocin, with both playing a role as a local, intra-ovarian factor that enhances the function of the <i>corpus luteum</i>.


2000 ◽  
Vol 80 (1) ◽  
pp. 1-29 ◽  
Author(s):  
Gordon D. Niswender ◽  
Jennifer L. Juengel ◽  
Patrick J. Silva ◽  
M. Keith Rollyson ◽  
Eric W. McIntush

The primary function of the corpus luteum is secretion of the hormone progesterone, which is required for maintenance of normal pregnancy in mammals. The corpus luteum develops from residual follicular granulosal and thecal cells after ovulation. Luteinizing hormone (LH) from the anterior pituitary is important for normal development and function of the corpus luteum in most mammals, although growth hormone, prolactin, and estradiol also play a role in several species. The mature corpus luteum is composed of at least two steroidogenic cell types based on morphological and biochemical criteria and on the follicular source of origin. Small luteal cells appear to be of thecal cell origin and respond to LH with increased secretion of progesterone. LH directly stimulates the secretion of progesterone from small luteal cells via activation of the protein kinase A second messenger pathway. Large luteal cells are of granulosal cell origin and contain receptors for PGF2αand appear to mediate the luteolytic actions of this hormone. If pregnancy does not occur, the corpus luteum must regress to allow follicular growth and ovulation and the reproductive cycle begins again. Luteal regression is initiated by PGF2αof uterine origin in most subprimate species. The role played by PGF2αin primates remains controversial. In primates, if PGF2αplays a role in luteolysis, it appears to be of ovarian origin. The antisteroidogenic effects of PGF2αappear to be mediated by the protein kinase C second messenger pathway, whereas loss of luteal cells appears to follow an influx of calcium, activation of endonucleases, and an apoptotic form of cell death. If the female becomes pregnant, continued secretion of progesterone from the corpus luteum is required to provide an appropriate uterine environment for maintenance of pregnancy. The mechanisms whereby the pregnant uterus signals the corpus luteum that a conceptus is present varies from secretion of a chorionic gonadotropin (primates and equids), to secretion of an antiluteolytic factor (domestic ruminants), and to a neuroendocrine reflex arc that modifies the secretory patterns of hormones from the anterior pituitary (most rodents).


Author(s):  
K.E. Krizan ◽  
J.E. Laffoon ◽  
M.J. Buckley

With increase use of tissue-integrated prostheses in recent years it is a goal to understand what is happening at the interface between haversion bone and bulk metal. This study uses electron microscopy (EM) techniques to establish parameters for osseointegration (structure and function between bone and nonload-carrying implants) in an animal model. In the past the interface has been evaluated extensively with light microscopy methods. Today researchers are using the EM for ultrastructural studies of the bone tissue and implant responses to an in vivo environment. Under general anesthesia nine adult mongrel dogs received three Brånemark (Nobelpharma) 3.75 × 7 mm titanium implants surgical placed in their left zygomatic arch. After a one year healing period the animals were injected with a routine bone marker (oxytetracycline), euthanized and perfused via aortic cannulation with 3% glutaraldehyde in 0.1M cacodylate buffer pH 7.2. Implants were retrieved en bloc, harvest radiographs made (Fig. 1), and routinely embedded in plastic. Tissue and implants were cut into 300 micron thick wafers, longitudinally to the implant with an Isomet saw and diamond wafering blade [Beuhler] until the center of the implant was reached.


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