Biomedical subjects
Publications and source records attributed to F Sánchez Franco.
A 65 year-old male with severe systolic mitral and tricuspid valve prolapse, associated with long-standing acromegaly is reported. The non published association could be caused by the effect of growth hormone on the valve connective tissue.
Diminished GH secretion is a well known association of obesity. As in obese humans, Zucker fatty rats develop a progressive GH deficiency, present at 6 weeks of age and maximal at 10 to 12 weeks. The aim of this study was to investigate the GH dependence of IGF-I gene expression in liver and extrahepatic tissues of the obese Zucker rat as a model of progressive GH reduction during adult life. Six- and 11-week-old obese Zucker rats and their lean littermates were used to compare body weight, glycemia, insulinemia, serum GH and IGF-I levels and IGF-I mRNA expression in liver, heart, aorta, kidney and skeletal muscle. In comparison with lean controls, obese Zucker rats showed at both ages comparable glycemia, severe hyperinsulinemia (mU/ml, mean+/-s.e.m.; 6 weeks 138+/-10 vs 45+/-6 P<0.001; 11 weeks 147+/-14 vs 46+/-3, P<0.001) and lower GH (ng/ml; 6 weeks 1.7+/-0.9 vs 2.7+/-1.1; 11 weeks 1.5+/-0.9 vs 4.2+/-1.2) in the presence of similar circulating IGF-I levels (ng/ml; 6 weeks 774+/-26 vs 694+/-28; 11 weeks 1439+/-182 vs 1516+/-121). Hepatic IGF-I mRNA expression was already reduced at 6 weeks of age due to a significant decrease in the IGF-Ib transcript compared with lean controls (relative units; IGF-Ia: 99+/-2% vs 100+/-5%; IGF-Ib: 69+/-10% vs 100+/-2%, P<0.05) and this reduction was more marked in 11-week-old animals when both IGF-I transcripts were significantly diminished (relative units; IGF-Ia: 80+/-6% vs 100+/-1%, P<0.05; IGF-Ib: 65+/-5% vs 100+/-2%, P<0.01). Extrahepatic tissues expressed almost exclusively the IGF-Ia transcript, the amount of which relative to controls was: (1) similar at 6 weeks and decreased at 11 weeks in kidney and skeletal muscle extracts (relative units; kidney: 6 weeks 88+/-10% vs 100+/-2%; 11 weeks 76+/-3% vs 100+/-4%, P<0.05; vastus lateralis: 6 weeks 95+/-7% vs 100+/-10%; 11 weeks 59+/-4% vs 100+/-2%, P<0.001); (2) similar at both ages in thoracic aorta (relative units; 6 weeks 121+/-6% vs 105+/-5%; 11 weeks: 91+/-14% vs 100+/-4%); and (3) increased at both ages in left ventricle extracts (relative units; 6 weeks 114+/-2% vs 99+/-9%, P<0. 05; 11 weeks 119+/-7% vs 95+/-3%, P<0.05). -specific dependence of IGF-I mRNA on GH levels during adulthood, reflected by the different behavior of IGF-I expression for each tissue in conditions of progressive decrease of GH levels.
The biosynthesis of growth hormone-releasing factor (GRF) by cerebrocortical tissue is controversial. Although several reports have indicated its presence in certain rat cortical areas and in cultured rat hypothalamic cells, no data exist demonstrating its biosynthesis in these areas. In this study, we have investigated the capacity of fetal rat cerebrocortical and hypothalamic cells in culture for synthesizing GRF. Fetal cerebrocortical and hypothalamic cells were exposed to [3H]Arg for 48 h. Medium and cell extracts were processed and [3H]Arg-IR-rGRF was isolated by affinity chromatography and characterized by HPLC. Intracellular [3H]Arg-IR-rGRF from both hypothalamic and cerebrocortical cells exhibited four major peaks, one of them coeluting with synthetic rGRF. In cerebrocortical cultures, newly synthesized and released [3H]Arg-IR-rGRF showed a similar pattern to the cell content. However, in media from hypothalamic cells, higher hydrophobicity molecular forms were absent. The data demonstrated that fetal cerebrocortical and hypothalamic cells in primary culture synthesize GRF with similar posttranslational processing, but with different molecular patterns of secretion.
The stimulatory effect of potassium depolarization upon somatostatin (SS) mRNA levels in primary cultures of fetal cerebrocortical cells was analyzed. Depolarizing stimuli, such as 56 mM K+ exposure for 30 min, elicited an increase in immunoreactive somatostatin (IR-SS) release to the media and decreased SS mRNA levels. These were increased when exposure to depolarization stimuli was prolonged up to 3 or more hr. At this time, potassium (30 and 56 mM) acted as a secretagogue, stimulating SS secretion, but was also effective in stimulating SS mRNA levels, suggesting that SS secretion can be coupled to SS mRNA accumulation. These changes were inhibited by the Ca2+ channel antagonist verapamil. In contrast, Na+ channel blockade by TTX did not modify the 24 hr potassium-induced increase in SS mRNA, although it partially abolished potassium-induced SS secretion. Examination of the rate of disappearance of SS mRNA levels after inhibition of mRNA transcription by actinomycin-D revealed that K+ stimulation of cerebrocortical cells stabilized the SS mRNA. These results suggest that the induction of SS mRNA expression by K+ is dose dependent, and involves the modulation of ion channels. The time-course study confirmed that the K(+)-induced SS mRNA accumulation is time dependent, chronic activation of the Ca2+ channels being necessary to stimulate SS gene expression. K+ stimulation may also increase the level of SS mRNA in cerebrocortical cells by reducing its rate of degradation.
Extensive studies exploring the regulation of hypothalamic somatostatin GHRIH release have been reported, but the factors regulating GHRIH release in the cerebral cortex have not been well defined. We have studied the effects of central neurotransmitters on GHRIH secretion by cultured fetal rat cerebral cortical cells and on intracellular GHRIH levels. Cells maintained in vitro for 15-20 days were incubated with dopamine (DA), acetylcholine (ACh), gamma-aminobutyric acid (GABA), norepinephrine (NE), serotonin (SE) or histamine (His) (10(-11) M to 10(3) M) for 30 minutes. Following incubation, immunoreactive GHRIH was measured by RIA in cell extracts and incubation media. DA increased intracellular GHRIH content but have no effect on GHRIH in the media. Both media and intracellular GHRIH content were significantly reduced by GABA and SE. The effect of NE was stimulatory at low (10(-9) M) and inhibitory at high (10(-5) M to 10(-3) M) concentrations. ACh was found to increase media GHRIH and to decrease intracellular GHRIH content; 30 min exposure to His did not significantly modify either media or intracellular GHRH. Our findings with fetal rat cerebral cortical cells in culture demonstrate that endogenous neurotransmitters do have the capacity to directly influence GHRIH regulation.
Information about growth hormone-releasing factor (GRF) regulation by somatostatin, GH and IGF-I is scarce and controversial. This could be due to the in vivo interactions among these signals and the lack of models for individualizing the action of one of them from the others upon GRF regulation. The aim of the present work was to study GRF regulation by these signals, using primary fetal rat hypothalamic-brain stem cell cocultures. Coculturing of these two cytotypes increases hypothalamic immunoreactive rat GRF (IR-rGRF) content in cells by 45% and in media by 36%. The effect of SS on GRF in cocultures was examined by using a multiple approach: (1) depleting endogenous SS by adding 1 mM cysteamine (CSH); (2) blocking endogenous SS by incubation with SS antiserum, and (3) incubating with synthetic SS14 at different concentrations and exposure periods. 1 mM CSH depleted IR-SS content (pg/plate, mean +/- SE) in cells (CSH-treated: 68 +/- 8 vs. control: 322 +/- 10, p < 0.01) and media (CSH-treated: 211 +/- 15 vs. control: 880 +/- 70; p < 0.01). In the CSH-induced SS-depleted cultures, a slight reduction in the IR-rGRF content in cells was observed (CSH-treated: 93.5 +/- 4.5 vs. control: 111 +/- 6; p < 0.05), with no effect on media content. When SS antiserum was added to plates, there was a slight reduction in the IR-rGRF content in cells and media, but it was not significantly different from the controls. However, SS14 (10(-10)-10(-8) M) could not modify IR-rGRF content in media and cells. The GH effect on IR-rGRF was studied in the absence of CSH and in CSH-induced SS-depleted cultures. GH (5 microM, 24 h) decreased (52%) the IR-rGRF content in media (GH-treated: 28.7 +/- 4.6 vs. control: 60.2 +/- 7; p < 0.01) without causing changes in cell content. In SS-depleted cultures, the inhibitory action of GH on media IR-rGRF was greater (62% decrease) (GH-treated: not detected, control 56 +/- 10; p < 0.01) and also affected IR-rGRF cell content (GH-treated: 64.3 +/- 7.3 vs. control: 160 +/- 9.6; p < 0.01). In the same experiments, GH increased IR-SS content in cells (GH-treated: 31.8 +/- 4.6 vs. control 20.9 +/- 0.5; p < 0.01) and in media (GH-treated: 413 +/- 7 vs. control: 286 +/- 9; p < 0.01). 1 mM CSH again depleted IR-SS content and abolished the GH stimulatory effect.(ABSTRACT TRUNCATED AT 400 WORDS)
To determine the possible physiological role of endogenous growth hormone-releasing factor (GRF) in the neuronal content and release of cerebral somatostatin (SS), we studied the effect of endogenous GRF blockade on the immunoreactive SS (IR-SS) content of cells and media in fetal rat cerebral cortical and hypothalamic cells in culture. Cells were cultured in minimum essential medium (MEM) with 10% fetal calf serum and 10% horse serum. After 7-10 days in vitro, media were replaced with MEM without sera containing anti-GRF immunoglobulins G (IgG) for 1, 5 or 24 h. Controls were incubated with equal amounts of IgG from normal rabbit serum (NRS). In another group of experiments, cells were incubated with GRF (10(-11) to 10(-7) M) for 1 or 24 h. Long-term exposure (24 h) to anti-GRF IgG resulted in decreased media and intracellular IR-SS content, in both cerebral cortical and hypothalamic cells. 24 h treatment with GRF caused a dose-dependent increase in the IR-SS content of cells and media, the stimulatory action being abolished by the addition of anti-GRF to plates containing 10(-7) M GRF. On the contrary, when cells were exposed to anti-GRF IgG for 1 h, IR-SS increased in the media as compared to the control group. Short-term incubation (1 h) with GRF (10(-9) to 10(-7) M) resulted in a dose-dependent inhibition of IR-SS content in the cells and media. This inhibitory action was partially prevented by the addition of anti-GRF to plates containing 10(-7) M GRF.(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of the present study was to ascertain whether sex differences exist in GH response to GHRH, and the influence that menstrual cycle have on this response. A GHRH test was performed on nine healthy men and ten women on days one and twelve of the menstrual cycle. Basal GH levels, (mean +/- SE) (7.98 +/- 3.09 ng/ml in women and 0.13 +/- 0.07 ng/ml in men, p less than 0.05) as well as maximal GH response (40.17 +/- 11.96 ng/ml in women and 9.63 +/- 2.32 ng/ml in males, p less than 0.01) were significantly higher in women than in men. In spite of a significant increase in estradiol levels during the menstrual cycle (75.88 +/- 2.48 pg/ml on day one and 198.40 +/- 28.65 pg/ml on day twelve, p less than 0.01) neither basal plasma GH levels, nor GH response to GHRH were significantly different. In conclusion, these results confirm that GH response to GHRH is higher in women than in men, and that this difference is not modified during the first phase of the menstrual cycle.
The effects of hypothyroidism duration on several factors implicated in GH secretion control were studied in the male rat at different maturity stages, ranging from the peripuberal period to adulthood. Thyroid ablation was performed on 22-day-old Wistar male rats maintained on a low iodine diet (T group). Age-paired controls (C group) were fed with the same diet, supplemented with potassium iodide. Subgroups of T and C animals (aged 32, 42, 52, 82 and 112 days) were studied 10, 20, 30, 60 and 90 days after surgery. After pentobarbital anesthesia, jugular blood was withdrawn before and 5 min after an intravenous TRH stimulus, for GH assay. Hypothalamic and pituitary tissues were obtained in order to measure GH, immunoreactive somatostatin (IR-SRIF) and growth hormone-releasing factor (IR-GRF). Growth rate and serum testosterone confirmed that C rats reached sexual maturity by day 30 of the study. Mean +/- SE serum GH (ng/ml) increased (p less than 0.05) in C animals from day 10 (38.5 +/- 5) to day 30 (67.4 +/- 7.3), with no significant variations thereafter. The same time sequence pattern was observed in pituitary GH concentrations. In T rats, both serum and pituitary GH decreased progressively from day 10 to 90, being significantly lower than in C at all times of the study. No GH response to TRH could be found in C groups. In contrast, GH increased significantly (p less than 0.05) in T animals after TRH at days 20 and 30.(ABSTRACT TRUNCATED AT 250 WORDS)
Chronic adrenal failure due to hypothalamic-hypophyseal disorders is rarely encountered. This can be due to hormonal deficiencies generally related to the presence of a brain tumor or an infiltrating process and sometimes to an isolated deficiency of ACTH. We report on two patients with adrenal failure with low basal cortisol levels and a poor response to short cortisol stimulation test with ACTH. Long cortisol stimulation test with ACTH was normal and ACTH was not stimulated with corticotropin releasing factor. However, other specific dynamic pituitary hormonal tests were normal. The uncommon clinical presentation of the disease, such as severe hypoglycemic crisis and fever of unknown origin (FUO), is underscored.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Most current evidence indicates that opiates act via the hypothalamus to influence pituitary function. There are no detailed studies concerning pituitary site of action. Direct action of opioids on gonadotropin secretion was studied using enzymatically dispersed rat pituitary cells maintained in a monolayer culture. A time course study demonstrated that pretreatment with beta h-endorphin (beta h-End) (10(-7) M) initiated an inhibitory effect on LH release at 24 h, and was more evident at 48 h. A dose dependent decrease in LH release by beta h-End in concentrations of 10(-9) M to 10(-7) M was shown, whereas FSH was unchanged. Equimolar concentrations (10(-7)M ) of methionine enkephaline (Met-Enk) and D-ala2-met-enkephalinamide (DALA) produced a significant decrease in LH. Naloxone (NAL) (10(-5)) enhanced the release of both LH and FSH, and also blocked the inhibitory effect of beta h-End on LH release. These results indicated that opioid peptides act directly on anterior pituitary cells, decreasing the release of LH, but not of FSH. NAL also had a direct effect increasing the release of LH and FSH, and blocking the inhibitory action of beta h-End.
This study was undertaken to determine the effect of opioid peptides and naloxone on the secretion of thyrotrophin (TSH), alpha subunit (alpha subunit) and beta thyrotrophin (TSH-beta) from rat pituitary dispersed cells in primary culture. Naloxone (NAL) 10(-5) M was found to increase basal TSH, alpha subunit and TSH-beta secretion. This effect of NAL was not blocked by human beta-endorphin (beta h-End) 10(-7) M. Concurrent treatment with triiodothyronine (T3) 10(-7) M significantly decreased NAL stimulated secretion of TSH and its subunits. Thyrotrophin releasing hormone (TRH) stimulation of secretion of TSH and its subunits was not further augmented by NAL. In contrast, 10(-7) M of beta h-End, methionine-enkephalin (Met-Enk) and D-ala2-met-enkephalinamide (DALA) had no effect on secretion of TSH and subunits. A time course study confirmed no change in TSH secretion following pre-treatment with beta h-End at 4, 10, 24 and 48 h. These findings go against a direct action of beta h-End, Met-Enk and DALA on TSH secretion. The response of TSH and its subunits to NAL and the lack of interaction with beta h-End might be explained by the existence of different types of opiate receptors. Counteraction of this effect by T3 suggests other possible mechanisms.
Explore the source record for details and available documents.
Consanguinity has been considered to be the major factor responsible for the high incidence of goiter in the area of Las Hurdes in Spain. However, iodine deficiency was later found to be severe enough to account for endemic goiter, and the presence of cretins in this area. Children from very similar family and socioeconomic backgrounds were found to be on three different nutritional programs, depending on the schools they were attending, and it appeared of interest to determine the effect of nutrition on the goiter incidence in children from the same population. Total iodine, nitrogen and creatinine concentrations were measured in casual urine samples. All three were found to change in parallel in the different subpopulations. They were low in schoolchildren receiving most of their meals at home. Such meals were composed of locally grown food. They were normal in children living in a boarding school, where all of the food is provided from outside the area. They were intermediate in children from a day care center, who received only some meals from an outside source. In the boarding school, goiter incidence was 21%, as opposed to 87% for schoolchildren fed at home. Such results indicate that in this area consanguinity plays a minor role, if any, in the high incidence of goiter.
Explore the source record for details and available documents.