Biomedical subjects

W C Duncan

Publications and source records attributed to W C Duncan.

At least 19 recordsLinked to original sources

PubMed2001

Evidence for a biological dawn and dusk in the human circadian timing system.

1. Because individuals differ in the phase angle at which their circadian rhythms are entrained to external time cues, averaging group data relative to clock time sometimes obscures abrupt changes that are characteristic of waveforms of the rhythms in individuals. Such changes may have important implications for the temporal organization of human circadian physiology. 2. To control for variance in phase angle of entrainment, we used dual internal reference points--onset and offset of the nocturnal period of melatonin secretion--to calculate average profiles of circadian rhythm data from five previously published studies. 3. Onset and/or offset of melatonin secretion were found to coincide with switch-like transitions between distinct diurnal and nocturnal periods of circadian rhythms in core body temperature, sleepiness, power in the theta band of the wake EEG, sleep propensity and rapid eye movement (REM) sleep propensity. 4. Transitions between diurnal and nocturnal periods of sleep-wake and cortisol circadian rhythms were found to lag the other transitions by 1-3 h. 5. When the duration of the daily light period was manipulated experimentally, melatonin-onset-related transitions in circadian rhythms appeared to be entrained to the light-to-dark transition, while melatonin-offset-related transitions appeared to be entrained to the dark-to-light transition. 6. These results suggest a model of the human circadian timing system in which two states, one diurnal and one nocturnal, alternate with one another, and in which transitions between the states are switch-like and are separately entrained to dawn and dusk. 7. This description of the human circadian system is similar to the Pittendrigh-Daan model of the rodent circadian system, and it suggests that core features of the system in other mammals are conserved in humans.

Body Temperature↗

PubMed2001

A circadian signal of change of season in patients with seasonal affective disorder.

BACKGROUND: In animals, the circadian pacemaker regulates seasonal changes in behavior by transmitting a signal of day length to other sites in the organism. The signal is expressed reciprocally in the duration of nocturnal melatonin secretion, which is longer in winter than in summer. We investigated whether such a signal could mediate the effects of change of season on patients with seasonal affective disorder. METHODS: The duration of melatonin secretion in constant dim light was measured in winter and in summer in 55 patients and 55 matched healthy volunteers. Levels of melatonin were measured in plasma samples that were obtained every 30 minutes for 24 hours in each season. RESULTS: Patients and volunteers responded differently to change of season. In patients, the duration of the nocturnal period of active melatonin secretion was longer in winter than in summer (9.0 +/- 1.3 vs 8.4 +/- 1.3 hours; P=.001) but in healthy volunteers there was no change (9.0 +/- 1.6 vs 8.9 +/- 1.2 hours; P=.5). CONCLUSIONS: The results show that patients with seasonal affective disorder generate a biological signal of change of season that is absent in healthy volunteers and that is similar to the signal that mammals use to regulate seasonal changes in their behavior. While not proving causality, this finding is consistent with the hypothesis that neural circuits that mediate the effects of seasonal changes in day length on mammalian behavior mediate effects of season and light treatment on seasonal affective disorder.

Adult↗

PubMed2001

Angiogenesis in the human corpus luteum: simulated early pregnancy by HCG treatment is associated with both angiogenesis and vessel stabilization.

BACKGROUND: This study examined changes in the luteal vasculature throughout the menstrual cycle and during simulated pregnancy with human chorionic gonadotrophin (HCG) in the human. METHODS: Endothelial cell and pericyte area were assessed by quantitative immunocytochemistry for CD34 and alpha-smooth muscle actin respectively, taking into consideration the dynamics of lutein cell hypertrophy and atrophy throughout the cycle and after HCG treatment. Endothelial cell proliferation was detected by Ki-67/CD34 dual staining and a proliferation index was obtained. The molecular regulation of angiogenesis was studied by examining changes in vascular endothelial growth factor (VEGF) immunostaining. RESULTS: The early luteal phase is associated with intense angiogenesis, as indicated by high endothelial cell proliferation, and by the mid-luteal phase a mature vasculature was apparent, as shown by maximal endothelial cell and pericyte areas. During the late luteal phase, decreased endothelial proliferation, endothelial cell and pericyte area indicated vascular regression. HCG treatment induced a second burst of total and endothelial cell proliferation and a concomitant increase in endothelial cell and pericyte areas. VEGF protein was expressed throughout the luteal phase and a significant increase was found after HCG treatment. CONCLUSION: Luteal rescue with HCG is associated with a second wave of angiogenesis and vascular stabilization.

Actins↗

PubMed2000

Angiogenesis in the human corpus luteum: localization and changes in angiopoietins, tie-2, and vascular endothelial growth factor messenger ribonucleic acid.

In the menstrual cycle, extensive angiogenesis accompanies luteinization. During luteolysis, endothelial cells die, whereas in a conceptual cycle, the corpus luteum (CL) persists, and endothelial cell survival is extended. A main stimulator for angiogenesis is vascular endothelial growth factor (VEGF), while the angiopoietins (Ang-1 and Ang-2) may be important modulators. The aim of this study was to investigate the localization of Ang-1, Ang-2, their common receptor Tie-2, and VEGF messenger ribonucleic acid (mRNA) at the different stages of the functional luteal phase and after rescue by hCG. Ang-1 mRNA was uniformly expressed at a low level throughout the CL. The signal was highest during the early luteal phase. In contrast, Ang-2 mRNA expression was localized strongly to individual granulosa and thecal luteal and endothelial cells. Administration of hCG was associated with an increase in the Ang-2 mRNA area of expression and grain density in individual luteal and endothelial cells. The Tie-2 receptor mRNA was localized in endothelial cells, and the area of expression was highest during the early luteal phase and during luteal rescue. VEGF mRNA was found exclusively in granulosa luteal cells, and the area of expression was highest in corpora lutea during simulated pregnancy. These results begin to characterize the molecular regulation of the divergent processes involved in luteal angiogenesis during luteinization, luteolysis, and rescue in the human and imply that the angiopoietins are involved during the initial angiogenic phase and in luteal rescue.

Adult↗

PubMed2000

Changes in insulin-like growth factor-binding protein-3 messenger ribonucleic acid in endothelial cells of the human corpus luteum: a possible role in luteal development and rescue.

In the human menstrual cycle, extensive angiogenesis accompanies luteinization; and the process is physiologically important for corpus luteum (CL) function. During luteolysis, the vasculature collapses, and the endothelial cells die. In a conceptual cycle, the CL persists both functionally and structurally beyond the luteoplacental shift. Although luteal rescue is not associated with increased angiogenesis, endothelial survival is extended. Despite the central role of the luteal vasculature in fertility, the mechanisms regulating its development and demise are poorly understood. There is increasing evidence that insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) may be important effectors of luteal function. Here, we have found that IGFBP-3 messenger RNA is expressed in the endothelium of the human CL and that the levels of message change during luteal development and rescue by human CG. The signal was strong during the early luteal phase, but it showed significant reduction during the mid- and late luteal phases. Interestingly, administration of human CG caused a marked increase in the levels of IGFBP-3 messenger RNA in luteal endothelial cells that was comparable to that observed during the early luteal phase. We conclude that endothelial cell IGFBP-3 expression is a physiological property of the CL of menstruation and pregnancy. These observations raise the intriguing possibility that the regulated expression of endothelial IGFBP-3 may play a role in controlling angiogenesis and cell responses in the human CL by autocrine/paracrine mechanisms.

Adult↗

PubMed2000

The human corpus luteum: remodelling during luteolysis and maternal recognition of pregnancy.

The marked tissue remodelling associated with luteolysis involves increased expression and activity of matrix metalloproteinases (MMPs) and an influx of immune cells, notably macrophages. Since the corpus luteum expresses high concentrations of specific tissue inhibitors of MMPs, it is clear that it is not only the increased activity of MMPs that is important, but also their tissue localization. Human chorionic gonadotrophin inhibits both MMP expression and macrophage influx in the rescued corpus luteum of early pregnancy. However, macrophages and the main cellular sources of MMPs in the corpus luteum do not express LH-hCG receptors. Therefore, it is likely that products of the steroidogenic cells, which do express LH-hCG receptors, are involved in the differential paracrine regulation of MMP expression and macrophage influx during luteolysis and maternal recognition of pregnancy.

Chorionic Gonadotropin↗

PubMed1999

5-HT agonist-induced phase-advances of the circadian pacemaker are diminished by chronic antidepressant drug treatment.

Serotonin (5-HT) and its agonists alter the timing of the circadian pacemaker. Previous research has shown that when they are injected 4 h before or after the onset of wheel-running, they phase-advance or delay, respectively, the timing of the pacemaker. Because serotonergic interventions alter 5-HT receptor number in the hypothalamus, we asked whether chronic treatment with an antidepressant drug (AD) that modifies serotonergic function could alter the phase-shifting effects of the 5-HT agonist 8-hydroxydipropylaminotetralin (8-OH-DPAT). Hamsters were treated chronically with the monoamine oxidase inhibitor (MAOI), clorgyline, and then injected with 8-OH-DPAT or vehicle (VEH) either 4 h before or after the onset of wheel-running. MAOI treatment decreased the magnitude of both 8-OH-DPAT- and VEH-induced phase advances, but not the magnitude of 8-OH-DPAT-induced phase-delays. The results indicate that 8-OH-DPAT-induced phase-advances and delays are functionally distinct with regard to adaptive changes during chronic AD treatment.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1999

Steroidogenic enzyme expression in human corpora lutea in the presence and absence of exogenous human chorionic gonadotrophin (HCG).

In a human conception cycle, the expected decline in progesterone production by the corpus luteum during the late luteal phase is prevented by human chorionic gonadotrophin (HCG) secreted by the implanting blastocyst. This study investigated the expression of components of the synthetic pathway for progesterone in human corpora lutea in the presence and absence of HCG in vivo. Corpora lutea were obtained from: (i) normally cycling women at the time of hysterectomy and classified on the basis of the urinary luteinizing hormone (LH) surge as early (n = 3), mid- (n = 3), or late luteal (n = 3); or (ii) women who had received daily doubling doses of HCG (n = 3) to 'rescue' the corpus luteum. Expression patterns of steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage (P450scc) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) were investigated by Northern blotting, in-situ hybridization and immunohistochemistry. Luteal 'rescue' with HCG was associated with the continued expression of these components. In the late luteal phase, in the absence of HCG, expression remained but was more variable. The expression of 3beta-HSD mRNA was significantly reduced during the luteal phase (P<0.01). In conclusion, during luteal 'rescue', HCG acts to maintain the steroidogenic pathway. In the absence of HCG, the decline in progesterone production begins in the presence of the main components of the steroidogenic pathway. While unlikely to initiate this decline, the altered expression levels of these components, particularly that of 3beta-HSD, may contribute to the continued reduction in progesterone production.

3-Hydroxysteroid Dehydrogenases↗

PubMed1998

Disruption of the activity-rest cycle by MAOI treatment: dependence on light and a secondary visual pathway to the circadian pacemaker.

The disruptive effects on the activity-rest cycle of the monoamine oxidase inhibitor (MAOI) clorgyline and of continuous light were examined in Syrian hamsters. When administered in dim and moderate light intensities, clorgyline delayed the daily onset of wheel-running. When administered in bright light, it dissociated the circadian rhythm of wheel-running. This dissociation was prevented by lesions of the intergeniculate leaflet of the ventral lateral geniculate nucleus. Constant darkness restored the circadian rhythm of wheel-running in hamsters with disrupted circadian rhythms. The phase of the restored rhythm of wheel-running was shifted 6-12 h later than the phase of wheel-running prior to dissociation. Our results suggest that MAOI treatment weakens the coupling between oscillators that comprise the circadian pacemaker, and augments the disruptive effects of continuous light acting via the intergeniculate leaflet region of the ventral lateral geniculate nucleus. These effects on the circadian pacemaker may be responsible for disruptions of the sleep-wake cycle that occur as side effects when MAOIs are used clinically to treat depression and might play a role in the induction of mania and rapid cycling by antidepressants.

Analysis of Variance↗

PubMed1998

The human corpus luteum: reduction in macrophages during simulated maternal recognition of pregnancy.

It has been shown that immune cells, particularly macrophages, accumulate in the corpus luteum during luteolysis. This study aimed to investigate the effect of maternal recognition of pregnancy on the localization and numbers of macrophages in the human corpus luteum. Corpora lutea (n = 12) were obtained from normally cycling women at the time of hysterectomy and were dated on the basis of serial urinary luteinizing hormone (LH) estimation. In addition, corpora lutea (n = 4) were collected from women who had received daily doubling doses of human chorionic gonadotrophin (HCG) to mimic the hormonal changes of early pregnancy. Macrophages were localized by immunohistochemistry using an anti-CD68 antibody. Steroidogenic cells, steroidogenic cells of thecal origin and endothelial cells were identified on serial sections by immunohistochemistry for 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase and von Willebrand factor, respectively. The luteal cells capable of responding directly to HCG were identified by isotopic in-situ hybridization for messenger RNA encoding LH/HCG receptors. Macrophages were localized primarily to the vascular connective tissue and theca-lutein areas of the corpus luteum, although some were found in the granulosa-lutein cell layer. Macrophage numbers increased throughout the luteal phase to a maximum in the late-luteal phase (P < 0.05). Luteal 'rescue' with HCG was associated with a marked reduction in the numbers of tissue macrophages when compared with those of the late-luteal phase (P < 0.001). One of the effects of HCG during maternal recognition of pregnancy is to prevent the normal influx of macrophages into the corpus luteum. As LH/HCG receptors localized to the steroidogenic cells, this implies a fundamental role for steroidogenic cell products in the control of macrophage influx into the human corpus luteum.

Cell Count↗

PubMed1998

Induced luteolysis in the primate: rapid loss of luteinizing hormone receptors.

The molecular mechanisms involved in luteolysis are still unclear in the primate. This study aimed to investigate the effect of induced luteolysis on the ovarian luteinizing hormone (LH) receptor and the steroidogenic enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the marmoset monkey. Luteolysis was induced in the mid-luteal phase either directly by systemic prostaglandin F2alpha (PGF2alpha), or indirectly by LH withdrawal using systemic gonadotrophin releasing hormone antagonist (GnRHant) treatment. The LH receptor was studied by isotopic mRNA in-situ hybridization and in-situ ligand binding and 3beta-HSD expression was studied using isotopic mRNA in-situ hybridization and immunohistochemistry. Induced luteolysis was associated with a reduction in the expression of LH receptor (P < 0.0001) and 3beta-HSD mRNA, closely followed by a reduction in the LH receptor (P < 0.05) and 3beta-HSD protein concentrations within 24 h. There were no differences in the findings whether luteolysis was induced with PGF2alpha or GnRHant. This study shows that disparate mechanisms to induce luteolysis in the primate result in an identical rapid loss of the LH receptor and 3beta-HSD. In conclusion, induced luteolysis leads to rapid loss of the steroidogenic pathway in luteal cells.

3-Hydroxysteroid Dehydrogenases↗

PubMed1998

Decreased sensitivity to light of the photic entrainment pathway during chronic clorgyline and lithium treatments.

Certain antidepressant drugs (ADs) cause disturbances in sleep that could result from their capacity to alter the timing of circadian rhythms. Effects on the timing of rhythms could be due to the drugs' known capacity to alter the frequency of the intrinsic rhythm of the circadian pacemaker, or to a capacity to modify the pacemaker's response to external stimuli that serve as time cues (Zeitgebers) that regulate the timing (phase) of its rhythm. To examine the possibility that ADs alter the sensitivity of the system that mediates the phase-shifting effects of light, hamsters were treated chronically with the MAOI, clorgyline, and lithium. Each hamster was then exposed to a single 5-min light pulse (intensity range = 0.00137 to 137 microW/cm2) at circadian phases known to elicit phase advances (CT18) and phase delays (CT13.5) in the daily onset of wheel running. The half-saturation constant (sigma), photic sensitivity (1/sigma), and maximum phase-shifting response to light were estimated from the best-fit stimulus response curves. In addition, threshold sensitivity, the light intensity required to produce a threshold phase-shifting response, was determined. Clorgyline decreased the magnitude of light-induced phase advances at each of the light intensities tested. Clorgyline also decreased the magnitude of light-induced phase delays at low light intensities, but increased the magnitude of phase delays at higher light intensities. Clorgyline decreased the sensitivity of the photic phase-shifting system, as indicated both by the threshold sensitivities at CT13.5 and CT18, and by 1/sigma at CT13.5. Lithium decreased the threshold sensitivity at CT18, and 1/sigma at CT13.5. Lithium decreased the magnitude of phase delays, but not phase advances. Clorgyline's effects on the photic entrainment pathway may be mediated by its effects on serotonin, which has been shown to modulate the pacemaker's response to morning and evening light, and by tolerance to this effect of serotonin. The fact that both clorgyline and lithium decrease the photic sensitivity of the entrainment pathway suggests that other psychoactive drugs might also share this property. It is possible that the decreased sensitivity to light of the entrainment pathway affects the clinical response to these and other psychoactive medications.

Adaptation, Physiological↗

PubMed1998

The effect of luteal "rescue" on the expression and localization of matrix metalloproteinases and their tissue inhibitors in the human corpus luteum.

Luteolysis is associated with tissue remodeling probably involving the matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs). This study investigated the expression and localization of the major MMPs and TIMPs in the human corpus luteum throughout the luteal phase and after luteal rescue with hCG. Corpora lutea (n = 9) were collected at hysterectomy and were dated by serial urinary LH estimation. In addition, corpora lutea (n = 3) were collected from women who had received daily doubling doses of hCG to mimic the hormonal changes of early pregnancy. MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 were investigated by zymography, reverse zymography, Northern blotting, and in situ hybridization. There was no change in the expression of MMP-1, TIMP-1, and TIMP-2 throughout the luteal phase or after luteal rescue. Little TIMP-3 could be detected in the corpus luteum. MMP-9 activity peaked in the early and late luteal phase. The expression and activity of MMP-2 were maximal in the late luteal phase. Exposure to hCG during luteal rescue in vivo was associated with a reduction (P < 0.05) in the expression and activity of MMP-2. Messenger ribonucleic acids (mRNAs) for MMP-1, MMP-2, and TIMP-2 were localized to the connective tissue stroma and the thecal-lutein cells of the corpus luteum. In contrast, TIMP-1 mRNA was localized to the granulosa-lutein cells, and MMP-9 mRNA was expressed in scattered cells within the steroidogenic and nonsteroidogenic cell layers. In conclusion, during maternal recognition of pregnancy, hCG prevents the normal increase in MMP-2 in the late luteal phase. MMPs can function in an environment containing large amounts of TIMP-1, as they have a different cellular localization.

Adult↗

PubMed1997

Increase of 5HT and VIP immunoreactivity within the hamster (Mesocricetus auratus) SCN during chronic MAOI treatment.

The effects of chronic treatment with the monoamine oxidase inhibitor (MAOI), clorgyline (CLG; 2 mg/kg per day) on serotonin (5HT) and vasoactive intestinal peptide (VIP) immunoreactivity (IR) within the hamster suprachiasmatic nucleus (SCN) were examined. Optical densities of 5HT IR and VIP IR were increased by MAOI treatment. VIP IR was increased in both the ventrolateral and dorsal regions of the SCN, suggesting that VIP content was increased within both perikarya and terminals of VIP neurons. The results suggest that previously described effects of MAOIs on the mammalian circadian system may be mediated in part, by their effects on serotonergic input to VIP neurons within the SCN.

Animals↗

PubMed1996

Circadian rhythms and the pharmacology of affective illness.

The chronic effects of antidepressant drugs (ADs) on circadian rhythms of behavior, physiology and endocrinology are reviewed. The timekeeping properties of several classes of ADs, including tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, serotonin agonists and antagonists, benzodiazepines, and melatonin are reviewed. Pharmacological effects on the circadian amplitude and phase, as well as effects on day-night measurements of motor activity, sleep-wake, body temperature (Tb), 3-methoxy-4-hydroxyphenylglycol, cortisol, thyroid hormone, prolactin, growth hormone and melatonin are examined. ADs often lower nocturnal Tb and affect the homeostatic regulation of sleep. ADs often advance the timing and decrease the amount of slow wave sleep, reduce rapid eye movement sleep and increase or decrease arousal. Together, AD effects on nocturnal Tb and sleep may be related to their therapeutic properties. ADs sometimes delay nocturnal cortisol timing and increase nocturnal melatonin, thyroid hormone and prolactin levels; these effects often vary with diagnosis, and clinical state. The effects of ADs on the coupling of the central circadian pacemaker to photic and nonphotic zeitgebers are discussed.

Animals↗

PubMed1996

Luteinizing hormone receptor in the human corpus luteum: lack of down-regulation during maternal recognition of pregnancy.

Luteal progesterone production is dependent on luteinizing hormone (LH) from the pituitary gland. Despite continuing LH secretion, the human corpus luteum undergoes functional luteolysis unless it is 'rescued' by human chorionic gonadotrophin (HCG), produced by the implanting blastocyst. As LH and HCG act through a common receptor, this study sought to determine the expression of the LH/ HCG receptor in the corpus luteum during maternal recognition of pregnancy. Corpora lutea were collected at hysterectomy from women in the normal luteal phase and after luteal 'rescue' with exogenous HCG. In each case the corpus luteum was classified according to the date of the LH surge measured in daily urine samples. The expression of the LH receptor was investigated by Northern blotting, in-situ hybridization and in-situ ligand binding. LH receptor mRNA and ligand binding activity were detected in corpora lutea from all stages of the luteal phase. LH receptor expression and binding were maintained during maternal recognition of pregnancy in the presence of exponentially increasing HCG concentrations. These data show that the LH receptor is maintained throughout the functional life-span of the human corpus luteum and is not down-regulated during maternal recognition of pregnancy.

Adult↗

PubMed1996

Measurement of circulating inhibin forms during the establishment of pregnancy.

This study investigated the forms of inhibin released into the circulation 1) in very early pregnancy, 2) after stimulation of the corpus luteum by exogenous hCG, and 3) in abnormal and failing human pregnancy. Samples were assayed by enzyme-linked immunosorbent assays for inhibin A, inhibin B, and inhibin pro-alphaC-related immunoreactivity (pro-alphaC-RI). The concentration of inhibin A rose steadily during the conception luteal phase to an initial peak 12 days after ovulation (104 +/- 23 pg/mL), then rose rapidly to a further peak 43 days after ovulation 424 +/- 6 pg/mL). The concentration of pro-alphaC-RI exhibited a much larger peak on day 15 after ovulation (1423 +/- 361 pg/mL), but fell thereafter. The concentration of inhibin B was low after ovulation and subsequently barely detectable in pregnancy. hCG treatment resulted in a significant rise in the concentrations of inhibin A and pro-alphaC-RI, but had no effect on the inhibin B concentration. The pro-alphaC-RI concentration was a better indicator of continuing pregnancy viability than either hCG or inhibin A. Early trophoblast secretes proportionately more bioactive inhibin than the corpus luteum. The corpus luteum and trophoblast do not secrete inhibin B into the circulation. These data support the concept of different physiological roles for different inhibin forms.

Abortion, Spontaneous↗

PubMed1996

Expression of tissue inhibitor of metalloproteinases-1 in the human corpus luteum after luteal rescue.

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a specific inhibitor of a group of proteolytic enzymes known as matrix metalloproteinases. These enzymes have been widely implicated in the process of tissue remodelling. Extensive remodelling occurs in the corpus luteum during luteolysis unless human chorionic gonadotrophin (hCG) is produced by the early conceptus. This study aimed to investigate the expression and localisation of TIMP-1 in human corpora lutea during the luteal phase of the cycle and after luteal rescue with exogenous hCG to mimic the changes of early pregnancy. Human corpora lutea from the early (n = 4), mid- (n = 4) and late (n = 4) luteal phases and after luteal rescue by hCG (n = 4) were obtained at the time of hysterectomy. Expression of TIMP-1 was investigated in these tissues by Western blotting, immunohistochemistry, Northern blotting and in situ hybridisation. Luteal cells of thecal origin were distinguished from those of granulosa origin by immunostaining for 17 alpha-hydroxylase. A 30 kDa protein consistent with TIMP-1 was detected in human corpora lutea. This protein was localised to the granulosa lutein cells in all tissues examined. TIMP-1 mRNA was found in large quantities in all glands examined and this again localised to the granulosa lutein cells. The expression and localisation of TIMP-1 did not change throughout the luteal phase and was not altered by luteal rescue. The function of this uniform expression of TIMP-1 in the corpus luteum is not clear but these data suggest that the inhibition of structural luteolysis during maternal recognition of pregnancy is not mediated by regulation of TIMP-1 expression.

Adult↗