Corpus Luteum Function in Early Pregnancy

Takai, Yoshimi; Strott, Charles A.; Marshall, John R.; Lipsett, Mortimer B.

doi:10.1210/jcem-29-2-225

Cited by 169 publications

(59 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Signal transduction by the LHR to G s can be tempered or desensitized as a consequence of arrestin2 (␤-arrestin1) binding to the receptor at the third intracellular (3i) loop (3). LHR desensitization occurs in ovarian follicles in response to the mid-cycle LH surge that promotes ovulation (4) and, based on serum progesterone levels, appears to occur in human corpora lutea in response to elevated levels of hCG during pregnancy (5).…”

Section: The Luteinizing Hormone/choriogonadotropin Receptor (Lhr)mentioning

confidence: 99%

Membrane Organization of Luteinizing Hormone Receptors Differs between Actively Signaling and Desensitized Receptors

Hunzicker-Dunn

Barisas

Song

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Signaling by the luteinizing hormone/choriogonadotropin receptor (LHR) is of considerable interest because of its requirement for successful reproduction. Time-resolved phosphorescence anisotropy and fluorescence resonance energy transfer were used to investigate the organization of endogenous LHRs in porcine follicular membranes in two distinct signaling states, active and desensitized. Desensitized LHRs exhibited ϳ3-fold slower rotational correlation times compared with active LHRs (59 ؎ 4 and 21 ؎ 9 s, respectively), suggesting that with agonist-dependent desensitization the receptors are organized into larger protein complexes. Incubation of membranes with inhibitors of LHR desensitization, such as neutralizing anti-arrestin antibodies, a synthetic peptide corresponding to the third intracellular loop of the LHR but not the corresponding scrambled peptide, or catalytically inactive ARNO, resulted in faster rotational diffusion times equivalent to those of actively signaling LHRs. Furthermore, desensitized LHRs exhibited a 2.4-fold increase in fluorescence resonance energy transfer between LHRs suggesting that the larger protein aggregates formed during desensitization contain more self-associated LHRs. These results indicate that agonist-dependent LHR desensitization precedes organization of LHRs at the cells surface into larger protein aggregates. The luteinizing hormone/choriogonadotropin receptor (LHR)1 is a seven transmembrane-spanning receptor coupled to G-proteins, most typically the stimulatory guanine nucleotide-binding proteins, which activate adenylyl cyclase to produce the second messenger signal, cAMP (1). Mechanisms involved in signal transduction by the LHR are of considerable interest because of the importance of the receptors in mammalian reproduction. In females, activation of the LHR regulates terminal follicular development and promotes ovulation and during pregnancy maintains progesterone production by the corpus luteum (2). In males, LHR signaling promotes testosterone production by Leydig cells (2). Signal transduction by the LHR to G s can be tempered or desensitized as a consequence of arrestin2 (␤-arrestin1) binding to the receptor at the third intracellular (3i) loop (3). LHR desensitization occurs in ovarian follicles in response to the mid-cycle LH surge that promotes ovulation (4) and, based on serum progesterone levels, appears to occur in human corpora lutea in response to elevated levels of hCG during pregnancy (5).The ␤ 2 -adrenergic receptor has served as a model for desensitization of G-protein-coupled receptors (GPCRs). Following agonist activation, desensitization of the ␤ 2 -adrenergic receptor is triggered by receptor phosphorylation catalyzed by a G-protein receptor kinase (6, 7). The G-protein receptor kinase phosphorylation sites on the ␤ 2 -adrenergic receptor facilitate interaction of the receptor with non-visual arrestins (8). Arrestins sterically hinder the ability of the receptor to activate G-proteins and thus moderate signal transduction by GPCRs (9, 10). Howe...

show abstract

Section: The Luteinizing Hormone/choriogonadotropin Receptor (Lhr)mentioning

confidence: 99%

Membrane Organization of Luteinizing Hormone Receptors Differs between Actively Signaling and Desensitized Receptors

Hunzicker-Dunn

Barisas

Song

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Specifically, a fall in insulin requirements in the first trimester may be mediated through a decline in progesterone, an anti-insulin hormone (7,24). The nadir of progesterone is at 8 weeks and remains below the peak level seen at week 4 until at least 16 weeks' gestation, reflecting the shift in progesterone secretion from the corpus luteum to the placenta (luteo-placental shift) (25)(26)(27). Preliminary data point to a temporal association between the decrease in plasma progesterone and glucose levels (12).…”

Section: Falling Insulin Requirement In Pregnancymentioning

confidence: 99%

Declining Insulin Requirement in the Late First Trimester of Diabetic Pregnancy

et al. 2001

View full text Add to dashboard Cite

OBJECTIVE -To investigate whether pregnancies complicated by type 1 diabetes are associated with a decrease in first-trimester insulin requirement.RESEARCH DESIGN AND METHODS -We examined the weekly insulin requirement (as units per kilogram per day) during the first trimester of pregnancy in diabetic women in the Diabetes in Early Pregnancy Study (DIEP) with accurate gestational dating, regular glucose monitoring, daily insulin-dose recording, and monthly glycohemoglobin measurements.RESULTS -In pregnancies that resulted in live-born full-term singleton infants, a significant 18% increase in mean weekly dosage was observed between weeks 3 and 7 (P ϭ 0.000), followed by a significant 9% decline from week 7 through week 15 (P ϭ 0.000). Further testing localized a significant change in insulin dose in the interval beginning weeks 7-8 and ending weeks 11-12 (P ϭ 0.014). Within this interval, the maximum decrease was between weeks 9 and 10 (mean), 10 and 11 (median), and 8 and 9 (most frequent maximal decrease). To determine whether prior poor glucose control exaggerated these trends, we categorized the women based on their glycohemoglobin values: Ͻ2 SDs above the mean of a normal population (subgroup 1), 2-4 SDs (subgroup 2), and Ͼ4 SDs (subgroup 3) at baseline. Late first-trimester declines in dosage were statistically significant in subgroup 2 (P ϭ 0.002) and subgroups 2 and 3 together (P ϭ 0.003). Similarly, women with BMI Ͼ27.0 had a greater initial insulin rise and then fall compared with leaner women. CONCLUSIONS -Observations in the DIEP cohort disclose a mid-first-trimester decline in insulin requirement in type 1 diabetic pregnant women. Possible explanations include overinsulinization of previously poorly controlled diabetes, a transient decline in progesterone secretion during the late first-trimester luteo-placental shift in progesterone secretion, or other hormonal shifts. Clinicians should anticipate a clinically meaningful reduction in insulin requirement in the 5-week interval between weeks 7 and 12 of gestation.

show abstract

“…Each hormone has a unique P-subunit, although the f-chain of hCG exhibits 81% homology with that of LH and may have arisen from the LH gene following duplication and readthrough in the 3' direction (Fiddes and Talmadge, 1984). In primates and equids, CG originates from the conceptus and rescues the corpus luteum by binding to an LH receptor (Yoshimi et al, 1969;Braunstein et al, 1976;Bolton et al, 1980). The lone fsubunit cannot bind to the LH receptor, the intact heterodimer being required for both binding and activation (Pierce and Parsons, 1981).…”

mentioning

confidence: 99%

The effects of beta-human chorionic gonadotrophin on the in vitro growth of bladder cancer cell lines

Gillott

Iles²,

Chard³

1996

Br J Cancer

View full text Add to dashboard Cite

Summary The effects of human chorionic gonadotrophin (hCG) and its subunits on in vitro bladder cancer cell growth have been assessed using the a tetrazolium salt reduction assay (MTT). Intact hCG, a-hCG and f,-core hCG all had no effect on cell growth, while fl-hCG increased MTT reduction in all four bladder cancer lines tested. The magnitude of ,B-hCG stimulation was maximal in the T24 line, which does not itself produce P-hCG and appeared to be correspondingly lower in ,B-hCG-secreting lines. The addition of antibodies to f,-hCG inhibited MTT reduction among high secretors but failed to inhibit MTT reduction in non-fl-hCG producers. These results are consistent with the poor prognosis associated with ,B-hCG expression by bladder tumours in vivo and suggest an autocrine/paracrine stimulation of tumour growth by endogenously produced f,-hCG.

show abstract

Corpus Luteum Function in Early Pregnancy

Cited by 169 publications

References 8 publications

Membrane Organization of Luteinizing Hormone Receptors Differs between Actively Signaling and Desensitized Receptors

Membrane Organization of Luteinizing Hormone Receptors Differs between Actively Signaling and Desensitized Receptors

Declining Insulin Requirement in the Late First Trimester of Diabetic Pregnancy

The effects of beta-human chorionic gonadotrophin on the in vitro growth of bladder cancer cell lines

Contact Info

Product

Resources

About