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Biomedical subjects

I R Young

Publications and source records attributed to I R Young.

At least 37 records · Page 2Linked to original sources
PubMed1999

Efficacy of the selective prostaglandin synthase type 2 inhibitor nimesulide in blocking basal prostaglandin production and delaying glucocorticoid-induced premature labor in sheep.

OBJECTIVE: The purpose of the study was to determine the effects of selective prostaglandin synthase type 2 inhibitors on basal prostaglandin concentrations in the fetal and maternal circulations and on the labor-associated increase in prostaglandin production in sheep. STUDY DESIGN: The effects of maternal nimesulide (0.01, 0.1, and 1 mg/kg) and 6-methoxy-2-naphthylacetic acid (1, 5, and 10 mg/kg) administration were examined (n = 5) at 134 +/- 1 days' gestation. At 138 days' gestation premature labor was induced by fetal dexamethasone infusion (1 mg/d). Ewes were treated with either vehicle or nimesulide infusion (20 mg. d-1. kg-1, n = 5 per group). RESULTS: Nimesulide and 6-methoxy-2-naphthylacetic acid decreased basal prostaglandin production in a concentration-dependent manner. Delivery of nimesulide-treated ewes was delayed by >/=17 hours with respect to that of control ewes (53.9 +/- 2.6 hours). In 2 nimesulide-treated ewes labor did not progress to delivery despite membrane rupture. The increase in prostaglandin concentrations usually seen during dexamethasone-induced labor was abolished in nimesulide-treated ewes and also in their fetuses. CONCLUSIONS: Highly selective inhibitors of prostaglandin endoperoxidase H synthase 2 may be required to spare fetal prostaglandin production and limit potential side effects during the suppression of preterm labor.

Animals↗
PubMed1999

Adrenal responsiveness and the timing of parturition in hypothalamo-pituitary disconnected ovine foetuses with and without constant adrenocorticotrophin infusion.

Ovine parturition results from an increase in foetal cortisol secretion in late gestation which is dependent on an intact hypothalamo-pituitary connection. The cortisol surge and parturition fails in hypothalamo-pituitary disconnected (HPD) foetuses but, paradoxically, immunoreactive (ir)-ACTH concentrations and secretory dynamics appear normal. This study compares the occurrence and timing of labour, basal ir-ACTH and cortisol concentrations and adrenal responsiveness in HPD foetuses (HPD/ACTH) receiving constant ACTH(1-24) infusion (43 ng/h/kg) from surgery (114+/-1 days gestational age (GA)) with those of saline-infused HPD or intact foetuses (HPD/SAL and INT/SAL). HPD/ACTH foetuses initiated labour at 147+/-2 days GA, which was not significantly different from INT/SAL foetuses (149+/-1 day GA). HPD/SAL foetuses were killed electively at 146+/-3 days GA with no signs of labour. Foetal ir-ACTH concentrations in all groups were indistinguishable, but only HPD/ACTH and INT/SAL foetuses had a significant cortisol surge. Adrenal responsiveness to ACTH(1-24)(1 microg/kg) was greater in HPD/ACTH foetuses than in HPD/SAL or INT/SAL foetuses at all GAs studied. Adrenal responsiveness in HPD/SAL foetuses exceeded that in INT/SAL foetuses at 120 and 130 days GA but did not change with GA. In summary, the basal cortisol and parturition defect in HPD foetuses was reversed by low-dose ACTH(1-24) infusion. Basal cortisol concentrations were unrelated to adrenal responsiveness. HPD/SAL foetuses had hyper-responsive adrenals compared to those of INT/SAL foetuses until 130 days GA, suggesting that the foetal hypothalamus exerts a negative influence on adrenal cortisol responses before 130 days GA, after which time stimulatory influences predominate.

Adrenal Glands↗
PubMed1999

Effect of labor induction on the expression of oxytocin receptor, cytochrome P450 aromatase, and estradiol receptor in the reproductive tract of the late-pregnant ewe.

UNLABELLED: In this study, we investigated the timing of changes in aromatase, estradiol receptor, and oxytocin receptor expression in ovine uterine and placental tissues before parturition. Labor was induced by betamethasone injection into the fetus on Days 130-132 of pregnancy. Tissue samples were collected at injection and then every 14 h until labor (56 h) from four ewes at each time point. Samples were analyzed for aromatase, estradiol receptor, and oxytocin receptor expression by in situ hybridization; for oxytocin binding to its receptor using a specific antagonist; and for estradiol receptor quantitation by immunocytochemistry. Aromatase mRNA expression increased by 14 h postinjection (p < 0.02) in the fetal villi and remained high until labor. Expression of estradiol and oxytocin receptor mRNAs was unchanged in myometrium but increased in the endometrial luminal epithelium by 28 h (p < 0.05) and remained high until labor. Estradiol receptor protein concentration increased modestly at labor while oxytocin receptor binding in the luminal epithelium changed in parallel to the mRNA concentration. IN CONCLUSION: 1) induction of aromatase may facilitate the expression of endometrial estradiol and oxytocin receptors in the placentome, 2) changes in endometrial rather than myometrial oxytocin receptor may be important in inducing parturition, and 3) the transcription of estradiol receptor and oxytocin receptor in the uterine epithelium are positively correlated during parturition.

Animals↗
PubMed1999

Pulsatile output of prostaglandin F(2alpha) does not increase around the time of luteolysis in the pregnant goat.

Prostaglandin (PG) F(2alpha) secreted from the uterus is the luteolysin of the estrous cycle and is also believed to be responsible for luteolysis in the pregnant doe at term. We have reported that basal progesterone concentrations decrease before basal PGF(2alpha) concentrations increase, which is inconsistent with this view. In this study we investigated whether luteolysis is associated with increased frequency or amplitude of pulsatile PGF(2alpha) secretion in does over the last 2 wk of gestation. Progesterone concentrations decreased approximately 1 wk before parturition. There was no accompanying increase in PGF(2alpha) concentrations or pulse frequency, and those pulses that were observed were of lesser amplitude and duration than those that have been associated with luteolysis in cycling ewes. A small increase in PGF(2alpha) pulse frequency was identified during the 3 days before parturition, but this was not associated with any change in progesterone concentrations. The biological significance of these small changes in PGF(2alpha) pulse frequency is obscure, although the high concentration of this eicosanoid at labor may have been related to the final, precipitous decline in plasma progesterone concentrations. These findings do not support the notion that PGF(2alpha) is the principal luteolysin in the pregnant doe at term.

Animals↗
PubMed1999

Design and use of internal receiver coils for magnetic resonance imaging.

This review describes coils for MRI that are inserted into the body through natural orifices. It covers the design and implementation of small internal receiver coils for use in the pelvis and gastrointestinal tract. Normal anatomy delineated by the high resolution obtained by using these coils and the appearances in a number of disease states for each clinical application are described.

Artifacts↗
PubMed1999

WWW as a teaching resource for introductory medical informatics in primary care.

This pro and contra report assesses the current state of the WWW as a teaching aid for Medical Informatics, using the experience gained from the delivery of a module to a heterogeneous group of health workers enrolled in an MSc/PgDip in Primary Care. The students were expected to act as both information consumers in a directed bibliographic retrieval task and information providers for Primary Care. The students' perceptions as to the usefulness and local relevance of current resources on the world wide web (WWW) are discussed.

Curriculum↗
PubMed1998

Two methods for semi-automated quantification of changes in ventricular volume and their use in schizophrenia.

Two semi-automated methods for quantification of ventricular volume change from baseline and follow-up magnetic resonance imaging scans have been developed. Technique 1 employs direct segmentation of the ventricles from both the scans using thresholding and contour extraction. Technique 2 operates on difference images produced by voxel based intensity subtraction of the baseline from the registered follow-up images. Here, all voxels with intensities above a noise threshold and in a restricted area are monitored to compute volumetric changes. In phantom measurements the first technique was accurate to 0.0046%, the second to 0.167% of the phantom volume. Results from normal volunteers was that the average ventricular volume changed by 1.52% and 1.54% for images acquired within 9 months using techniques 1 and 2, respectively. With schizophrenic patients mean change of 10.78% and 9.43% were found employing the first and second procedures, respectively. All measurements agreed with a radiologist's visual grading of the changes. Robust, objective, fast, easy-to-use, and fairly accurate procedures have been developed and validated to quantify volumetric changes.

Adult↗
PubMed1998

Fetal and maternal endocrine changes approaching parturition in the goat: lack of evidence for prostaglandins E2 and F2alpha as signals for luteolysis.

We investigated the temporal relationship of fetal cortisol secretion to circulating concentrations of fetal ACTH1-39 and its high-molecular weight precursors in goats. We also measured the concentrations of progesterone, estradiol-17beta estrone sulfate, prostaglandin (PG) E, PGF2alpha, and PGF2alpha metabolite (PGFM) in maternal arterial plasma over the last month of gestation. Prostaglandin concentrations were also measured in utero-ovarian venous plasma. There was a positive association between ACTH1-39 in fetal plasma and the prepartum surge in fetal cortisol that commenced 8 days before labor. The fetal cortisol surge was followed by a simultaneous decrease in maternal progesterone and an increase in plasma estrogens commencing 3-4 days before labor. No change in basal prostaglandin concentration occurred before this time. There was a positive veno-arterial difference of PGE and PGF2alpha across the uterine vascular bed, confirming the uteroplacental unit as a major source of these eicosanoids in the plasma of the pregnant doe. We conclude that the fetal signal for parturition precedes luteolysis by some 5 days and find no evidence of changes in the basal concentrations of PGE and PGF2alpha in maternal plasma at the time of luteolysis.

Adrenocorticotropic Hormone↗
PubMed1998

Angiotensin II infusion in vivo does not modulate cortisol secretion in the late-gestation ovine fetus.

Maturation of the fetal adrenal gland is critical for the onset of ovine parturition. It has long been proposed that the fetal adrenal gland may be under inhibitory influences during late gestation. In vitro evidence has suggested that angiotensin II may be such an inhibitory factor and may help to prevent a premature increase in cortisol concentrations. The aim of this study was to test the effect of angiotensin II infusion in vivo on basal cortisol concentrations and fetal adrenal responsiveness to an ACTH-(1-24) challenge. Fetuses received a continuous infusion of either angiotensin II (100 ng . min-1 . kg-1; n = 7) or saline (2 ml/h; n = 4), which commenced at 140 days of gestation (GA) and continued for a total of 50 h. Adrenal responsiveness to the administration of ACTH-(1-24) (5 microg/kg) was determined during angiotensin II or saline infusions at both 2 and 48 h after infusion onset. Angiotensin II had no significant effect on adrenal responsiveness after acute (2 h) or chronic (48 h) infusion. There was no effect of saline or angiotensin II infusion on basal immunoreactive ACTH or cortisol concentrations after 2 h, but there was a significant increase in basal cortisol concentrations in both treatment groups by 48 h, probably reflecting the normal rise in cortisol concentrations at this GA. Mean arterial blood pressure was significantly increased in angiotensin II-infused fetuses only. This study has therefore found no evidence to suggest that angiotensin II infusion in vivo modulates fetal basal cortisol concentrations or adrenal responsiveness in the last week of gestation, in contrast with previous in vitro studies. These results throw into question the proposed role of angiotensin II as a negative modulator of adrenal function in the ovine fetus.

Adrenal Glands↗
PubMed1998

Hypothalamo-pituitary disconnection of the late-gestation ovine fetus results in profound changes in cortisol secretion that are not reflected in commensurate changes in adrenocorticotropin secretion.

A prepartum increase in fetal glucocorticoid concentrations is essential for the perinatal transition to extrauterine life for many mammalian species. In the case of the sheep, this increase in cortisol is also the trigger for parturition, and depends upon an intact hypothalamo-pituitary unit. Fetal sheep that have undergone hypothalamo-pituitary disconnection (HPD) fail to have a prepartum cortisol surge or initiate labor, despite apparently normal fetal ACTH concentrations in late gestation. We have investigated whether a defect exists in the regulation of pulsatile neurohormone secretion in the pituitaryadrenal axis of the HPD sheep fetus, by comparing immunoreactive (ir) ACTH and cortisol secretory dynamics in intact and HPD fetuses at 126 and 145 days of gestation (normal gestation length, 147 days). The fetal surgery was conducted at 115 days of gestation. Blood samples were collected at 5-min intervals for 2 h on each experimental day, and the resulting irACTH and cortisol concentrations were analyzed by multiple-parameter deconvolution and cross-correlation analysis. Basal irACTH secretion was less (P < 0.01) in HPD fetuses than intact fetuses at 126 days, but it had recovered by 145 days. There were no differences in irACTH half-life or the number or duration of irACTH secretory bursts between the two groups of fetuses or the two gestational ages (GAs). The size of the irACTH secretory bursts was not affected by the operation, but it increased with GA to a similar extent in both groups of fetuses (P < 0.01). In keeping with the observations for irACTH secretion, there was no effect of age or the operation on cortisol half-life or on the number or duration of cortisol secretory bursts. In contrast, there were dramatic age-related increases (P < 0.01) in the basal cortisol secretion rate and the size of the cortisol secretory bursts in the intact, but not the HPD, fetuses. Cross-correlation analysis revealed a significant (P < 0.01) concordance between irACTH and cortisol secretion in only the intact fetuses at 126 days; this was not apparent in the intact fetuses at 145 days, or in the young or old HPD fetuses. These findings confirm a major defect in cortisol secretion in the late-gestation HPD fetus but suggest that this is not caused by defects in irACTH secretion. Together with other observations, these data suggest that ACTH may not be the sole, or primary, regulator of adrenal cortisol secretion in the late-gestation ovine fetus.

Adrenocorticotropic Hormone↗
PubMed1998

Studies on the role of ACTH in the regulation of adrenal responsiveness and the timing of parturition in the ovine fetus.

A dramatic late-gestation increase in fetal plasma cortisol concentrations is critical for the timing of parturition in the sheep. This increase appears to depend upon an intact hypothalamo-pituitary unit and is characterised by increasing responsiveness of the fetal adrenal gland to ACTH. ACTH has been postulated as the critical determinant of the late-gestation cortisol increase; however, recent evidence has suggested that other factors, including the ACTH precursor, pro-opiomelanocortin, may also be involved. To further define the role of ACTH in determining the timing of parturition and the responsiveness of the fetal adrenal gland, intact (INT/ACTH) and hypophysectomised (HX/ACTH) fetuses received a continuous infusion of ACTH(1-24) from the time of surgery (approximately 115 days gestational age (GA)) at a rate we have previously shown to generate normal fetal cortisol concentrations and term parturition in HX fetuses. A third group of saline-infused intact fetuses (INT/SAL) served as the control group. Adrenal responsiveness was assessed by cortisol responses to ACTH(1-24) challenges at 120, 130 and 140 days GA. There were no differences between the three groups of fetuses in the timing of parturition, the late-gestation increase in cortisol concentrations or the size of the adrenal cortex. In both INT/SAL and INT/ACTH fetuses, there were significant increases in basal immunoreactive-ACTH concentrations with advancing GA, although no such increase was observed in HX/ACTH fetuses. The proportion of total ACTH immunoreactivity present in low molecular weight (LMW) forms in INT/ACTH fetuses was greater than that in INT/SAL fetuses, while the level of LMW ACTH in HX/ACTH fetuses was intermediate. Both ACTH(1-24)-infused groups of fetuses had dramatically enhanced adrenal responsiveness to ACTH(1-24) at all GAs tested when compared with INT/SAL fetuses and there was a correlation (in rank order) between the proportion of LMW ACTH immunoreactivity and adrenal responsiveness. From these observations it appears that there is a separate regulation of adrenal responsiveness from basal cortisol concentrations and that an increase in basal cortisol concentrations can occur in the absence of an increase in basal ACTH concentrations. Furthermore, an increase in adrenal responsiveness does not appear to predict the timing of parturition nor basal cortisol concentrations. Taken together with previous studies it appears that ACTH plays an essential role in maintaining the growth of the fetal adrenal and enhancing its responsiveness, but a late-gestation increase in ACTH concentrations is not required to regulate basal cortisol concentrations or the timing of parturition.

Adrenal Glands↗
PubMed1997

Source of inhibin in ovine fetal plasma and amniotic fluid during late gestation: half-life of fetal inhibin.

Immunoactive inhibin (ir-inhibin) concentrations were determined in chronically catheterized sheep between 120 and 145 days gestation. Maternal plasma ir-inhibin concentrations remained basal (0.19 +/- 0.05 ng/ml) throughout the period of study. Immunoactive inhibin concentrations in male and female fetal plasma were elevated above those observed in maternal plasma, with the concentrations in plasma of male fetuses (7.38 +/- 0.04 ng/ml) being significantly greater (p < 0.001) than those in female fetuses (1.07 +/- 0.14 ng/ml). The concentrations of ir-inhibin in amniotic fluid of ewes bearing male fetuses (10.93 +/- 1.55 ng/ml) were significantly greater than in ewes bearing female fetuses (2.81 +/- 0.32 ng/ml; p < 0.05) but not significantly different from the concentrations in male fetal plasma. Immunoactive inhibin concentrations decreased following surgery in gonadectomized fetuses, to 3.25 +/- 0.99 ng/ml within 6 h, and remained at a mean value of 0.75 +/- 0.38 ng/ml from 24 h after gonadectomy. The half-life of circulating inhibin in fetal plasma, estimated from the decay curve during the first 6 h after surgery, was 3.94 +/- 0.88 h. There was a significant (p < 0.05) decrease in the concentration of ir-inhibin in amniotic fluid after gonadectomy; however, this decrease occurred gradually over 7 days, and ir-inhibin concentrations did not fall to those concentrations observed in fetal circulation at any time after gonadectomy. It is concluded that the major source of circulating ir-inhibin in male fetal plasma, but not in amniotic fluid, is the gonads.

Amniotic Fluid↗
PubMed1997

Photoperiodic history and hypothalamic control of prolactin secretion before birth.

We investigated whether the fetal lamb can construct a photoperiodic history in utero. We measured the fetal PRL response to a 12-h photoperiod in intact fetal sheep and in fetal sheep after hypothalamo-pituitary disconnection (HPD), following exposure of the ewe to either a long (16 h L) or short (8 h L) photoperiod for 50 days in early pregnancy. Ewes were maintained on either a long light (LL, n = 20) or a short light (SL, n = 19) regimen from 57 days gestation until fetal HPD (pre-LL, n = 7; pre-SL, n = 7) or sham surgery (pre-LL, n = 13; pre-SL, n = 12) was performed at 99-113 days gestation. All ewes were housed in a 12-h photoperiod from surgery until 140 days gestation. In HPD fetal sheep previously exposed to SL, fetal PRL concentrations were significantly higher (P < 0.05) after 20 days in the 12-h L regimen than previously (0-5 days, 3.2 +/- 0.6 ng/ml; 21-25 days, 5.6 +/- 1.4 ng/ml). In the HPD fetal sheep previously exposed to LL, however, fetal PRL concentrations significantly decreased (P < 0.05) after 5 days exposure to the 12-h L regimen (6.7 +/- 2.9 ng/ml) and remained low throughout the remaining study period (31-35 days, 1.7 +/- 0.5 ng/ml). In contrast, in the sham group there was no effect of photoperiodic history on the gestational age profile of fetal PRL, and PRL concentrations increased significantly (F = 22.4, P < 0.001) in fetal sheep previously exposed to either SL or LL. Fetal PRL concentrations were significantly higher (P < 0.05) after 121 days gestation in the 12-h L regimen in all sham fetal sheep (<110 days, pre-SL 6.4 +/- 0.3 ng/ml, pre-LL 12.0 +/- 3.3 ng/ml; 121-125 days, pre-SL 20.0 +/- 3.9 ng/ml, pre-LL 25.9 +/- 4.4 ng/ml). TRH (50 microg) was administered i.v. to all fetal sheep at 130-134 days gestation. There was a significant fetal PRL response to TRH in both the HPD (F = 20.9, P < 0.001) and sham (F = 31.3, P < 0.001) groups. There was no difference, however, in the PRL response to TRH in fetal sheep previously exposed to SL or LL in either the HPD or sham groups. The maximum percentage changes in PRL occurred at +10 min after TRH administration in the HPD (pre-SL, 421 +/- 75%; pre-LL, 555 +/- 76%) and sham groups (pre-SL, 394 +/- 68%; pre-LL, 369 +/- 59%). In summary, therefore, we have demonstrated that there is an effect of photoperiodic history on the PRL response to an intermediate photoperiod in utero in HPD fetal sheep. It appears, however, that the effect of photoperiodic history on PRL secretion in intact fetal sheep is either masked or suppressed by the stimulatory effect of factors associated with an increase in gestational age acting at the fetal hypothalamus.

Animals↗
PubMed1996

Plasma catecholamine and met-enkephalin-Arg6-Phe7 responses to hypoxaemia after adrenalectomy in the fetal sheep.

We have investigated whether removal of the fetal adrenal glands alters the effect of acute hypoxaemia on the circulating concentrations of noradrenaline, adrenaline, Met-Enkephalin and Met-Enkephalin-Arg6-Phe7 (MERF) in the late gestation sheep fetus. Ewes of 6 adrenalectomized and 9 intact fetuses were subjected to a 30 min period of hypoxaemia and a 30 min period of normoxaemia between 135 and 141 days gestation. Removal of the fetal adrenals abolished the fetal adrenaline response and significantly reduced the fetal noradrenaline response to hypoxaemia. There was no significant increase in circulating Met-Enkephalin during either hypoxaemia or normoxaemia in either the intact and adrenalectomized groups. During basal conditions, plasma concentrations of MERF were significantly greater in the adrenalectomized group (1.64 +/- 0.07 ng/ml) than in the intact fetal sheep (1.04 +/- 0.05 ng/ml). There were significantly greater changes (p < 0.05) in plasma MERF concentrations during hypoxaemia than during normoxaemia in both the intact and adrenalectomized groups. Plasma concentrations of MERF were inversely correlated with arterial PO2 (r = -0.44, p < 0.01) in the adrenalectomized but not the intact group of fetal sheep during hypoxaemia. We have demonstrated therefore that the fetal adrenal is the major source of circulating catecholamines, but not Met-Enkephalin or MERF during hypoxaemia in late gestation. The increase in circulating MERF concentrations after adrenalectomy may reflect compensatory changes in the synthesis and/or secretion of MERF in developing sympathetic neurones.

Adrenalectomy↗
PubMed1996

Growth and differentiation of fast and slow muscles in fetal sheep, and the effects of hypophysectomy.

1. Isometric contractile characteristics of fast-twitch (flexor digitorum longus, FDL; medial gastrocnemius, MG) and slow-twitch (soleus) muscles were determined in pentobarbitone-anaesthetized fetal sheep between 90 and 140 days gestation. Five fetuses were hypophysectomized (HPX) at 90-95 days gestation and then studied at 138-140 days. 2. At 90-95 days gestation the time to peak of single twitch contractions for the soleus, MG and FDL were not significantly different from each other; the mean value (+/-S.E.M.) for all the muscles at this age was 77.6 +/- 9.0 ms. At 120-125 days gestation the MG and FDL contracted significantly faster (44.0 +/- 0.9 and 40.8 +/- 1.8 ms, respectively) than at 90-95 days, and did not change significantly thereafter. In contrast, the soleus muscle contracted more slowly (111.9 +/- 6.6 ms) at 138-140 days than at 90-95 days and 120-125 days gestation. 3. Soleus muscle consisted of type I fibres at all gestational ages. There was no significant change with gestational age in the relative numbers of type I and II fibres in the MG and FDL, but in the diaphragm the number of type I fibres increased and the number of type II fibres decreased between 125 and 138 days gestation. 4. HPX abolished the normal increase of soleus weight relative to body weight between 125 and 138 days but did not alter the change of twitch contraction time with age. HPX significantly prolonged twitch time to peak and time to half-relaxation of MG and time to half-relaxation of FDL at 138 days. 5. The maximum rate of rise of the isometric tetanic contraction was unchanged by HPX in all three hindlimb muscles, but fatigue of MG and FDL was increased. 6. The relative proportions of different fibre types in the hindlimb muscles and the diaphragm were unchanged by HPX, but there was a significant decrease in mean areas of type I and II fibres in the FDL and MG of the HPX fetuses.

Animals↗
PubMed1996

The role of the pituitary-thyroid axis in the developmental regulation of enkephalin-containing peptides in the superior cervical ganglia and adrenal of the fetal sheep.

We have postulated that sympathetic neurones may be one source of circulating enkephalins in the fetus. Therefore, we have investigated the effects of increasing gestational age on the content of the enkephalin-containing peptides in the superior cervical ganglia (SCG) of the fetal sheep during late gestation. We have also investigated the role of the pituitary-thyroid axis in the coordinate regulation of enkephalin-containing peptides within the fetal sympathoadrenal system. We found an increase (P < 0.05) in the content of Free Met-O-Enkephalin between 85 and 105 days (d) (0.46 +/- 0.12 nmoles/SCG) and 116 and 125 d (0.93 +/- 0.12 nmoles/SCG), and the SCG content of Free Met-O-Enkephalin remained elevated throughout the remainder of gestation. The fetal SCG content of Total Met-O-Enkephalin also increased significantly between 85 and 105 d (2.8 +/- 0.5 nmoles/SCG) and 116 and 125 d (7.1 +/- 1.2 nmoles/SCG). There was, therefore, no change in the ratio of Total:Free Met-O-Enkephalin content of the SCG between 85 and 145 d. There were no significant effects of fetal hypophysectomy with or without thyroxine (T4) replacement on the content of Free Met-O-Enkephalin (intact, 1.11 +/- 0.18 nmoles; hypophysectomy (HX) + Sal, 1.41 +/- 0.25 nmoles; HX + T4, 1.08 +/- 0.27 nmoles) or Total Met-O-Enkephalin (intact, 3.03 +/- 0.90 nmoles; HX + Sal, 4.03 +/- 0.22 nmoles; HX + T4, 3.53 +/- 0.88 nmoles) in the fetal SCG. The adrenal contents of Free and Total Met-O-Enkephalin were, however, significantly reduced after fetal hypophysectomy and these effects were not altered by replacement with T4 after fetal hypophysectomy. In summary, we have demonstrated for the first time that enkephalin-containing peptides are present in the SCG of the fetal sheep and that the SCG enkephalin content increases between 85 and 125 days gestation. We have found no evidence that there is a change in the post-translational processing of the enkephalin precursor to Free Met-Enkephalin within the SCG during the second half of gestation. In contrast to the fetal SCG, maintenance of adrenal enkephalin content in late gestation is dependent on the presence of an intact fetal pituitary, but is independent of the circulating concentrations of thyroxine.

Adrenal Glands↗
PubMed1996

Thyroxine replacement after hypophysectomy alters the pattern of enkephalin localisation in the adrenal medulla of the fetal sheep.

It has been suggested that a pituitary-derived or -dependent factor may suppress enkephalin peptide synthesis in the central noradrenaline- containing cells of the sheep adrenal medulla in late gestation. We have investigated the effect of thyroxine (T4) replacement after fetal hypophysectomy on the localisation of enkephalin peptides within the peripheral adrenaline- and central noradrenaline-containing regions of the adrenal medulla of the fetal sheep. Fetal hypophysectomy (HX) was performed in 12 fetal sheep at 105-108 days gestation (term = 145 +/- 3 days gestation). T4 (40 micrograms/kg/24h) (HX + T4) or saline (HX + Sal) were infused between 110 and 140 days gestation. Adrenal glands were collected from the HX + T4, HX + Sal groups and from a group of intact fetal sheep (n = 4) for immunohistochemistry using anti- met-enkephalin and an avidin-biotin staining system. In adrenals from intact fetal sheep, there was intense positive staining for met-enkephalin in the peripheral adrenaline-containing region and sparse staining for enkephalins in the central noradrenaline-containing region. In contrast, in the HX + Sal group, enkephalin staining was uniformly present throughout the peripheral and central regions of the adrenal medulla. In the HX + T4 group, however, the staining density of met-enkephalin was higher within the adrenaline cells of the peripheral rim of the medulla than in the central medullary region. We have demonstrated that T4 replacement after fetal hypophysectomy restores the normal ontogenetic pattern of localisation of enkephalin peptides within the fetal adrenal. We postulate that T4 acts either indirectly via neural mechanisms or directly at the noradrenaline-containing cells to mediate the suppression of enkephalin staining within the central noradrenaline-containing region of the adrenal medulla of the fetal sheep in late gestation.

Adrenal Medulla↗