Biomedical subjects

C Dieguez

Publications and source records attributed to C Dieguez.

At least 199 records · Page 11Linked to original sources

PubMed1986

Thyroid function in patients with hyperprolactinaemia: relationship to dopaminergic inhibition of TSH release.

It has been reported recently that patients with hyperprolactinaemia may develop hypothyroidism as a consequence of the increased inhibition of TSH release by dopamine which occurs in the majority of such patients. In this study we have evaluated thyroid function in a large number of hyperprolactinaemic patients in order to delineate more precisely the relationship between thyroid status, free thyroid hormone levels and the control of TSH release by dopamine. Biochemical euthyroidism was present in the majority of the hyperprolactinaemic patients. Our data indicate that the increased dopaminergic inhibition of TSH release does not lead to hypothyroidism. Instead, the slightly elevated basal TSH levels and TSH responses to TRH (within the normal range) may reflect the operation of a compensatory mechanism to maintain euthyroidism in the face of te increased inhibition of TSH release by hypothalamic dopamine.

Adult↗

PubMed1986

Influence of dopaminergic, adrenergic and cholinergic blockade and TRH administration on GH responses to GRF 1-29.

In order to establish the influence of dopaminergic, alpha-adrenergic and cholinergic pathways on GRF-mediated GH release we have studied the GH responses to GRF 1-29 (100 or 50 micrograms as i.v. bolus) alone and in combination with metoclopramide (MCP, 10 mg, i.v.), thymoxamine (THYM, 210 micrograms/min, 150 min infusion), and atropine (1.2 mg, i.v.). We have also investigated any possible interaction between TRH and GRF in view of the reported inhibitory effects of TRH infusion on stimulated GH release. Dopaminergic and alpha-adrenergic blockade with MCP and THYM respectively, did not have any effect on the GH responses to GRF. This lack of effect strongly suggests that any action which these neurotransmitters may exert on GH secretion is not at a pituitary level. TRH did not modify the GH response to GRF suggesting that the inhibitory effect on stimulated GH secretion is exerted at a hypothalamic level. In contrast, GH responses to GRF were significantly reduced by prior administration of atropine. These data support the view that cholinergic pathways play an important role in the regulation of GH secretion and such control may be exerted at both hypothalamic and pituitary levels.

Adult↗

PubMed1986

Thyrotropin regulates thyrotroph responsiveness to dopamine in vitro.

The effect of conditioned vs. fresh culture medium on the dopaminergic inhibition of TSH and PRL secretion by primary cultures of male rat anterior pituitary cells has been studied. In the presence of conditioned medium (that had been in contact with the cells over the 3-day culture period) 10(-6) M dopamine (DA) inhibited PRL secretion by 50% and TSH secretion by 30%. After 4 h of incubation with fresh medium 10(-6) M DA still inhibited PRL secretion by 50% but increased TSH release by 20%. TSH release was rapid and could be prevented by 10(-6) M prazosin, an alpha 1 adrenoreceptor antagonist. Fresh medium did not alter TRH induced TSH release. In parallel cultures and under identical conditions fresh medium reduced [3H]dihydroergocryptine (DHE) binding to DA receptors from 2.5 +/- 0.4 fmol/10(5) cells to 0.95 +/- 0.3 fmol/10(5) cells (means +/- SEM, n = 5, P less than 0.001). The effect of fresh medium was dose dependent against the dopaminergic inhibition of TSH secretion and against DA receptor binding. If 1 mU TSH was included, in fresh medium, the dopaminergic inhibition of TSH secretion remained unchanged and [3H]DHE binding to DA receptors did not fall. The rank order of potency of thyroid stimulators was bovine TSH (21 U/mg) greater than semipurified bovine TSH (Thytropar, 1.4 U/mg) greater than endogenous rat TSH (0.03 U/mg expressed as NIADDK-rat TSH-RP2) greater than Graves' immunoglobulin G (0.01 U/mg) when either DA or bromocriptine was used as the dopaminergic agonist. When anterior pituitary cells from hypothyroid rats were examined, the effects of culture medium on the dopaminergic inhibition of TSH and on DA receptor binding were approximately twice those observed in normal cells, but the inclusion of 1 mU TSH in the fresh medium completely prevented the loss of DA function and binding. PRL, human CG, ACTH, insulin, glucagon, and heat-inactivated TSH were unable to prevent the effect of medium replacement on dopaminergic inhibition of TSH and DA receptor binding. The data suggest a mechanism whereby TSH may control its own secretion via DA.

Adrenocorticotropic Hormone↗

PubMed1986

Hypothalamic D2 receptors mediate the preferential release of somatostatin-28 in response to dopaminergic stimulation.

We have studied the effect of dopamine (DA) together with agonist and antagonist drugs of varying specificity on the release of immunoreactive forms of somatostatin (SS) from the perfused, adult rat hypothalamus in vitro. Levels of SS increased from 14.7 +/- 3.7 pg (mean +/- SE) under basal conditions to 137 +/- 23.0 pg after exposure to 10(-6) M DA. This dopaminergic effect was mimicked by the specific D2 agonists bromocriptine (10(-7) M) and LY 171555 (10(-6) M) but not by the D1 agonist SKF 38393A (10(-6) M). The stimulatory action of DA (10(-6) M) was blocked by the active (d) but not the inactive (l) isomer of butaclamol (10(-7) M). Similar blockade was achieved with the specific D2 antagonists metoclopramide (10(-8) M) and domperidone (10(-8) M), whereas the D1 antagonist SCH 23390 partially blocked the stimulation of DA but only when used at X100 greater concentration (10(-6) M). SCH 23390 (10(-8) M) did not affect the dopaminergic stimulation of SS release. HPLC characterization of the immunoreactive forms of SS yielded two peaks which corresponded to SS-28 and SS-14. The ratio of these forms varied significantly under different conditions. In the basal state the ratio of SS-28 to SS-14 was 1:4.4; in response to stimulation with DA, the ratio was 1:1.7 and in response to depolarization with 60 mM K+ the ratio was 1:3.1. In conclusion, the stimulatory action of DA on SS release is mediated via hypothalamic D2 receptors. Furthermore dopaminergic stimulation increases the molar ratio of SS-28 to SS-14 in the total immunoreactive SS which is released.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1986

Atropine blockade of growth hormone (GH)-releasing hormone-induced GH secretion in man is not exerted at pituitary level.

The role of acetylcholine (Ach) in the regulation of human GH secretion was assessed using atropine, which selectively blocks cholinergic muscarinic receptors. Paired tests were performed in seven normal subjects using GH-releasing hormone (GHRH) 1-44 (1 microgram/kg iv), with and without atropine pretreatment (1 mg im). The GHRH 1-44-induced GH secretory peak [20.7 +/- 4.5 (SEM) ng/ml] was completely blocked by atropine administration (2.3 +/- 0.6 ng/ml) (P less than 0.01). To determine whether this atropine blockade was at the pituitary level, a series of in vitro studies were conducted using monolayer cultures of cells from bovine anterior pituitary glands. GHRH 1-44 (10(-8) M) stimulated bovine GH release (11.1 +/- 1.5 micrograms/ml) as compared to control values (5.1 +/- 0.4 microgram/ml) (P less than 0.01). This response was not altered by 10(-6) M atropine (14.9 +/- 0.9 microgram/ml). Similar results were obtained with GHRH, 10(-9) M, with or without atropine, 10(-7) M. Addition of 10(-6) M Ach to the incubation medium significantly increased bovine GH release (12.7 +/- 1.2 microgram/ml) and the effect of 10(-6) M Ach and 10(-8) M GHRH was additive (20.9 +/- 2.1 micrograms/ml) (P less than 0.01). Similar results were obtained with Ach, 10(-5) M, and GHRH, 10(-9) M. Atropine or eserine alone did not alter basal GH secretion, and atropine blocked Ach-stimulating activity. In conclusion, atropine blockade of GHRH-induced GH secretion appears to be exerted at a site other than pituitary.

Acetylcholine↗

PubMed1986

Growth hormone responses to growth hormone-releasing factor (1-29) in euthyroid, hypothyroid and hyperthyroid rats.

In order to investigate whether the impaired GH secretion associated with hypothyroidism and hyperthyroidism is due to a hypothalamic or a pituitary disorder, we have studied plasma GH responses to GH-releasing factor (1-29) (GRF) in euthyroid, hypothyroid and hyperthyroid rats. Hypothyroid rats showed a significant (P less than 0.001) reduction in GH responses to GRF (5 micrograms/kg) at 5 min (350 +/- 35 vs 1950 +/- 260 micrograms/l), 10 min (366 +/- 66 vs 2320 +/- 270 micrograms/l) and 15 min after GRF injection (395 +/- 72 vs 1420 +/- 183 micrograms/l; mean +/- S.E.M.) compared with euthyroid rats. Hyperthyroid rats showed a significant (P less than 0.05) decrease in GH responses to 5 micrograms GRF/kg after 30 min (200 +/- 14 vs 325 +/- 35 micrograms/l) but not at other time-points, or after the administration of 1 microgram GRF/kg. These data indicate that in hypothyroidism and perhaps hyperthyroidism there is an alteration in the responsiveness of the somatotroph to GRF administration.

Animals↗

PubMed1986

Effects of thyroid status on brain catecholamine biosynthesis in adult rats: assessment by a steady-state method.

Effects of thyroid status on brain catecholamine turnover in adult rats were investigated using a steady-state method. Rats were treated for 3 weeks with s.c. injections of L-thyroxine (0.4 mg/kg), aminotriazole in drinking water (0.1%, w/v) or vehicle. After 2 weeks of treatment rats were implanted chronically with lateral intracerebroventricular (i.c.v.) cannulae. They were injected i.c.v. with [3H]tyrosine 1 week later. Catecholamine and tyrosine content and specific activity were measured in mediobasal hypothalamus, anterior hypothalamus and striatum, using high-performance liquid chromatography with electrochemical detection. Thyroxine treatment resulted in a significant increase in noradrenaline and dopamine synthesis localized to the mediobasal hypothalamus. Conversely, aminotriazole treatment resulted in a significant decrease in noradrenaline synthesis localized to the mediobasal hypothalamus. The localization of these changes in catecholamine turnover to the mediobasal hypothalamus suggests that they may be specific functional effects which are of importance in the overall integrated control of thyroid function.

Amitrole↗

PubMed1985

Differential effects of acute DA receptor blockade with domperidone on LH and TSH release in patients with hyperprolactinemia.

Since dopamine (DA) has been implicated in the inhibitory control of both TSH and LH, we have compared TSH and LH levels following dopamine (DA) receptor blockade with domperidone in patients with hyperprolactinemia due to presumed prolactinomas. Eight euthyroid patients (aged 19-37 yr) with presumed prolactinomas each received domperidone (10 mg iv) at 11:00 and 23:00 h and tests were separated by at least one week. Basal TSH levels were significantly greater at 23:00 than at 11:00 h (2.7 +/- 0.5 vs 1.7 +/- 0.4 mU/l, mean +/- SE, p less than 0.01) whereas basal LH levels did not differ. All subjects showed clear rises in basal TSH levels following drug administration and these were significantly greater at 23:00 than at 11:00 h (p less than 0.02 at each time point). In contrast there was no alteration in LH levels following drug administration at either time of day. These data suggest that the mechanisms underlying the dopaminergic control of TSH and LH are different in these patients. Furthermore the data argue against an anterior pituitary or median eminence site of action of DA in the inhibition of LH release in hyperprolactinemia since domperidone does not penetrate the blood brain barrier to any appreciable extent.

Adult↗

PubMed1985

An in vivo steady-state method for the determination of catecholamine biosynthesis in the rat brain using high-performance liquid chromatography with electrochemical detection.

A technique is described for the measurement of steady-state catecholamine (CA) synthesis in the rat brain in vivo, using [3H]tyrosine incorporation with high-performance liquid chromatography (HPLC) and electrochemical detection. Adult male rats chronically implanted with lateral intracerebroventricular (i.c.v.) cannulas, were injected i.c.v. with [3H]tyrosine. CA and tyrosine content and specific activity were measured in mediobasal hypothalamus, anterior hypothalamus and striatum. A time-dependent increase in CA synthesis occurred in all tissues over 20 min post-i.c.v. injection. The technique described may prove to be useful in the assessment of central neurotransmitter turnover in various physiological and pharmacological settings.

Animals↗

PubMed1985

The effects of cholinergic blockade on the growth hormone and prolactin response to insulin hypoglycaemia.

The effect of cholinergic blockade on growth hormone (GH) and prolactin (PRL) secretion during insulin-induced hypoglycaemia was assessed in six normal male volunteers (mean age 23, age range 21-25). Each subject underwent two insulin tolerance tests with and without atropine. GH responses were significantly lower 45 min after insulin administration with atropine (17.5 +/- 2.5 mU/l (mean +/- SEM) than with placebo (37.6 +/- 3.6 mU/l, P less than 0.0006). In contrast PRL responses were higher (P less than 0.01) at 45 and 90 min after insulin during treatment with atropine. These data demonstrate that cholinergic mechanisms are involved in stimulatory and inhibitory pathways in the medication of the respective GH and PRL responses to insulin induced hypoglycaemia in man.

Adult↗

PubMed1985

The influence of oestrogens on the sensitivity of PRL, TSH and LH to the inhibitory actions of dopamine in hyperprolactinaemic patients.

The effects of oestrogen priming on the response of serum PRL, LH and TSH to dopamine (DA) infusion have been studied in hyperprolactinaemia. Seven hyperprolactinaemic females (aged 22-57 years; basal PRL 911-5130 mU/l, normal less than 420 mU/l), had submaximal DA infusions (0.06 micrograms/kg/min) over 3 h. The DA was repeated at the same dose after pretreatment with ethinyl oestradiol (E2) 100 micrograms daily by mouth for 3 d, and after a further 2 week interval, following pretreatment with tamoxifen (TAM) 20 mg twice a day by mouth for 3 d. Ethinyl oestradiol pretreatment stimulated a rise in basal PRL levels in all subjects (mean +/- SE, mU/l; 2903 +/- 761 vs 2293 +/- 684, P less than 0.05) while TAM produced a higher but more variable increase in basal PRL levels (mean +/- SE, mU/l; 3402 +/- 757, P = n.s.). The individual increments in basal PRL levels after both E2 and TAM pretreatment showed a significant positive correlation with the greater decrement in PRL levels during E2 and TAM primed DA infusions (E2, r = 0.93, P less than 0.01, TAM, r = 0.83, P less than 0.05). E2 pretreatment produced a rise in basal LH levels in 5/7 patients, and there was a significant positive correlation between the rise in basal LH levels after E2 and the decremental change in LH levels in E2 primed DA infusions (r = 0.94, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Lack of effect of the TRH related dipeptide histidyl-proline diketopiperazine on TSH and PRL secretion in normal subjects, in patients with microprolactinomas and in primary hypothyroidism.

We have studied the effects of the TRH related dipeptide histidyl-proline diketopiperazine [cyclo (His-Pro)] on basal and stimulated TSH and PRL secretion in normal volunteers, in patients with microprolactinomas and in patients with primary hypothyroidism. Cyclo (His-Pro), 400 micrograms intravenously did not alter basal TSH or PRL levels in normal males and females and was also without effect upon the elevated basal TSH and PRL levels in patients with primary hypothyroidism and microprolactinomas respectively. The same dose of cyclo (His-Pro) did not affect the TSH or PRL response to TRH (100 micrograms i.v.) in normal male volunteers. These data indicate that cyclo (His-Pro) does not affect TSH and PRL secretion in man at this dosage. It is also unlikely that this molecule will be of any therapeutic benefit in states of hyperprolactinaemia.

Adult↗

PubMed1985

Relationships between the circadian rhythms of TSH, prolactin and cortisol in surgically treated microprolactinoma patients.

Pharmacological doses of glucocorticoids inhibit TSH release both in vivo and in vitro and since the circadian rhythms of TSH and cortisol show a reciprocal relationship, the hypothesis has been advanced that changes in cortisol levels may be a primary determinant of circadian TSH changes. We have tested this hypothesis by studying the relationship between circadian cortisol and TSH rhythms in subjects before and during blockade with metyrapone. Seven patients were studied during their routine post-operative assessment following selective transethmoidal adenomectomy for microprolactinomas. PRL levels were restored to normal (less than 420 mU/l) in all patients by surgery (pre-op: 930-2752 mU/l, post-op: 33-376 mU/l) and the patients also had normal pituitary function in other respects. Blood was sampled hourly for 24 h before and on the third day of treatment with metyrapone (250 mg, 2 hourly). In order to compare circadian rhythms, hormonal data were subjected to cosinor analysis which involved fitting of the data with a cosine function using the method of least squares. The 6% cross reactivity of the cortisol antibody with 11-deoxycortisol was taken into account during the calculation of results. All subjects showed a normal cortisol rhythm which was strikingly blunted during metyrapone treatment. Group mean (+/- SD) TSH mesors, amplitudes and acrophases for control and metyrapone treated subjects were 1.5 +/- 0.26, 1.29 +/- 0.48; 0.46 +/- 0.26, 0.23 +/- 0.13 and -49 degrees +/- 9.8 degrees; -62 degrees +/- 2.7 degrees respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

The effects of thyroid hormone deprivation in vivo and in vitro on growth hormone (GH) responses to human pancreatic (tumor) GH-releasing factor (1-40) by dispersed rat anterior pituitary cells.

Anterior pituitary cells from euthyroid and hypothyroid male rats have been cultured as monolayers for 3 days with or without 5 nM T3 and stimulated with either human pancreatic GH-releasing factor 1-40 (hpGRF), TRH, or the Ca2+ channel ionophore A23187. Basal GH secretion was reduced in the hypothyroid cultures (P less than 0.001) and basal TSH secretion increased (P less than 0.001). Culture with T3 increased GH secretion and intracellular GH content in euthyroid and hypothyroid cultures but suppressed TSH secretion with no effect on intracellular TSH content in either euthyroid or hypothyroid cultures. hpGRF released more GH from euthyroid [3.52 +/- 0.2 (SE) micrograms/6 h X 10(5) cells] than hypothyroid cultures of (0.17 +/- 0.01 micrograms/6 h X 10(5) cells, P less than 0.001) without a change in ED50 (approximately 0.02 nM). The reduction in hpGRF-induced GH release remained significant when corrected for the reduced intracellular GH content in the hypothyroid cultures. hpGRF-induced GH release also declined relative to A23187-induced GH release in hypothyroid cultures. Culture with 5 nM T3 doubled maximum hpGRF-induced GH release in euthyroid cultures and increased maximum release 10-fold in hypothyroid cultures without altering the ED50 of hpGRF action. In contrast, T3 suppressed TRH-induced TSH release in euthyroid cultures but was without effect on TRH-induced TSH release in the hypothyroid cultures. T3 did not effect the ED50 of TRH action (2-5 nM). In summary, hypothyroid rat anterior pituitary cells in culture have a reduced maximal GH response to hpGRF, but the same ED50. hpGRF activity can be partially restored by physiological concentrations of T3 in vitro.

Animals↗

PubMed1985

Alpha 1-adrenoreceptors and alpha 1-adrenoreceptor-mediated thyrotropin release in cultures of euthyroid and hypothyroid rat anterior pituitary cells.

TSH responses to adrenergic agonists have been measured in 3-day monolayer cultures of euthyroid and hypothyroid male rat anterior pituitary (AP) cells. Responses were qualitatively similar in that (-)epinephrine and (-)norepinephrine had the same ED50 in each culture (ED50 = approximately 6 and 16 nM, respectively) and demonstrated the same alpha 1-adrenergic specificity. Hypothyroid cultures secreted approximately twice as much TSH per cell as euthyroid cultures over the 2-h experimental period. (-)Epinephrine produced a 95 +/- 8% (mean +/- SE) release of TSH relative to basal secretion in euthyroid cultures and only 62 +/- 7% release in the hypothyroid cultures (P less than 0.01). The comparable figures for (-)norepinephrine were 62 +/- 7% and 38 +/- 5%, respectively (P less than 0.05). In absolute terms, adrenergic agonists released the same amount of TSH from euthyroid and hypothyroid cultures. In contrast, TRH (and the Ca+2 channel ionophore A23187) released twice as much TSH from the hypothyroid cells as in the euthyroid cultures. Epinephrine-induced TSH release was significantly impaired (P less than 0.001) when either euthyroid or hypothyroid cells were cultured without thyroid hormones. In contrast, TRH-induced TSH release was enhanced (P less than 0.001) in the euthyroid cultures. [3H]Dihydroergocryptine [( 3H]DHE) was used to quantify alpha 1-adrenoreceptors on the same cell preparations as those used to derive the functional data (see above). Prazosin (1 microM) was used to define nonspecific binding of [3H]DHE. Specific binding to euthyroid cells had a Kd of 5.8 +/- 4 nM and a maximum binding capacity of 2.2 +/- 0.4 fmol/10(5) cells (n = 5). In parallel cultures of hypothyroid cells, the Kd (6.2 +/- 5 nM) was not significantly different, whereas the maximum binding capacity (1.4 +/- 0.3 fmol/10(5) cells) was significantly reduced (P less than 0.05). Adrenergic compounds showed a rank order of potency of prazosin greater than (-)epinephrine greater than or equal to (-)norepinephrine greater than or equal to yohimbine greater than clonidine against the binding of 5 nM [3H]DHE to euthyroid and hypothyroid cells. The amount of [3H]DHE binding per cell that each adrenergic compound was able to displace at saturating concentrations was less in hypothyroid cells than in euthyroid cells. There was no change in the ED50 values of these compounds in the same experiments.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1985

The influence of lithium chloride on experimental autoimmune thyroid disease.

Lithium administration is known to be associated with the development of thyroid dysfunction; it also exerts an effect on the immune system. The effect of lithium on experimental autoimmune thyroid disease was studied in female August rats. Following immunization with rat thyroglobulin in Freund's complete adjuvant, lithium chloride was administered i.p. for 30 days to four groups at varying stages of the disease. Control animals received i.p. saline. Anti-thyroglobulin antibody levels (measured by ELISA) were significantly increased in rats given lithium immediately post-immunization (group B) compared to control animals (661 +/- 42 OD vs 448 +/- 68; mean +/- s.e., P less than 0.02). In contrast, animals which received lithium during the spontaneous resolution of the disease (group D) showed a significant fall in anti-TG antibody compared to controls (99 +/- 15 vs 27 +/- 15; P less than 0.001). Anti-TG antibody levels remained undetectable in animals which received lithium but were not immunized. The splenic T cell blastogenic response (as measured following phytohaemagglutinin stimulation) was significantly increased in rats receiving lithium prior to and during immunization (group A) (stimulation index 63.4 +/- 6.9 vs 10.2 +/- 2.4; P less than 0.001). Spontaneous cell proliferation of splenic lymphocytes was decreased in two lithium treated groups (group A P less than 0.005, group C P less than 0.05). There was no alteration in splenic weight or the degree of thyroid lymphocytic infiltration in any of the treated group. Lithium exerted both positive and negative influences on the immune system in rats immunized with thyroglobulin in adjuvant but did not induce autoantibody production in normal rats.

Animals↗

PubMed1985

The influence of cyclosporin A on the induction of experimental autoimmune thyroid disease in the PVG/c rat.

Using an experimental model of autoimmune thyroid disease we have investigated the influence of cyclosporin A (CyA) on the induction of the disease and its potential ability to prevent disease development. PVG/c rats (n = 80) neonatally thymectomized (day 21) and thence sublethally irradiated were divided into eight groups and received either no CyA or oral CyA (10 mg/kg body weight) for varying periods prior to and during disease induction. Serial serum measurements of thyrotropin (TSH) by radioimmunoassay and anti-thyroglobulin autoantibody by enzyme linked immunosorbent assay showed a progressive rise in untreated animals. The rise in serum TSH levels from 349 +/- 15 ng/ml (mean +/- s.e., normal less than 400 ng/ml) at 7 weeks of age to 526 +/- 61 ng/ml at 11 weeks and 820 +/- 54 ng/ml at 15 weeks was not significantly different in animals treated with CyA for periods ranging from 24 h prior to thymectomy to 7 days post-thymectomy. In contrast animals treated for 28 days post-thymectomy showed significantly lower levels of TSH at both 11 weeks (391 +/- 26; P less than 0.02) and 15 weeks (587 +/- 37; P less than 0.005) as compared with untreated animals. Similar though less dramatic changes were seen in intermediate groups. Autoantibody levels in untreated animals rose from initially undetectable levels to 0.451 +/- 0.07 OD (mean +/- s.e.) at 11 weeks and 0.581 +/- 0.041 OD at 15 weeks. Animals treated for at least 4 weeks after thymectomy with CyA had significantly lower levels of antibody at both 11 weeks (0.213 +/- 0.01; P less than 0.001) and 15 weeks (0.337 +/- 0.03; P less than 0.001) of age. Intermediate groups ranged in antibody levels depending on the duration of CyA treatment. Thyroid gland weight (12.7 +/- 2.4 mg/100 g body weight, mean +/- s.e.) and histological grade of thyroiditis (1.8 +/- 0.4, mean +/- s.e.) in the animals treated with CyA for 4 weeks, assessed when the animals were killed at 15 weeks, were smaller and had less severe thyroiditis than untreated thymectomized and irradiated animals (23.8 +/- 2.8 mg/100 g, P less than 0.02 and 2.9 +/- 0.2, P less than 0.05) killed at the same time. CyA given for long enough during induction of experimentally-induced autoimmune thyroid disease delayed the onset of disease and reduced its severity but could not prevent it given over time courses ranging from 48 h prior to thymectomy to 4 weeks after.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1984

The effects of long term growth hormone releasing factor (GRF 1-40) administration on growth hormone secretion and synthesis in vitro.

The ability of human pancreatic GH releasing factor 1-40 (hpGRF 1-40) to release GH has been studied in rat anterior pituitary cells in primary culture. Over 24 hours hpGRF (1-40) increased total (cell content and secretion) production 2-fold with an ED50 of 20 pM. Subsequent hpGRF (1-40) stimulation of GH release was not affected by pretreatment when the fall in stored GH was taken into account. In contrast LH responses to gonadotrophin releasing hormone (GnRH) were markedly desensitized after 24 hours GnRH pretreatment in the same experimental system and using the same analysis. hpGRF (1-40) responses were not desensitized when pretreatment was for 3, 12 or 24 hours. The data show that hpGRF (1-40) responses do not desensitize in our experimental conditions under which GnRH responses show marked desensitization.

Animals↗