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Biomedical subjects

E R Hernandez

Publications and source records attributed to E R Hernandez.

At least 19 recordsLinked to original sources

Avoiding multiple pregnancies: sailing uncharted seas.

Single embryo transfer is being proposed as the solution to avoid multiple pregnancies in IVF. Nevertheless, in my opinion, although this is the right solution, it is still not the correct one at the present time. Mainly, it is unfair to the majority of infertile couples and it will also severely limit the physician's capacity to resolve unfavourable IVF cases. Furthermore, current IVF technology is far from perfect and the impact of single embryo transfer needs to be evaluated in patients over 38 years of age, poor responders, and also in regard to blastocyst transfer and the development of pre-implantation genetic diagnosis.

Embryo Transfer↗

Embryo implantation and GnRH antagonists: embryo implantation: the Rubicon for GnRH antagonists.

When gonadotrophin-releasing hormone (GnRH) was discovered, the agonist and antagonist of GnRH were developed to control the release of FSH and LH by the gonadotrophs. More than 10 years of research were needed to develop a GnRH antagonist free of histamine release. Recent studies have shown that these GnRH antagonists are effective in preventing a rise in LH during ovarian stimulation in IVF. However, a decrease in ongoing pregnancies seems to suggest that implantation rates per transferred embryo are reduced in GnRH antagonist-stimulated cycles. In my opinion, these data highlight an area less well known to clinicians: the role of the GnRH antagonist at the cellular level in extrapituitary tissues. There are sufficient data in the literature suggesting that GnRH antagonist is an inhibitor of the cell cycle by decreasing the synthesis of growth factors. Given that, for folliculogenesis, blastomere formation and endometrium development, mitosis is everything; the interaction between the GnRH antagonist and the GnRH receptor (present in all these cells and tissues) may compromise the mitotic programme of these cells. This is the Rubicon for the GnRH antagonist: to demonstrate irrevocably that, at the minimal doses necessary to suppress LH release, it does not affect processes such as implantation, embryo development and folliculogenesis.

Animals↗

Growth hormone does not increase the expression of insulin-like growth factors and their receptor genes in the pre-menopausal human ovary.

A growing body of information now supports the existence of a complete intraovarian insulin-like growth factor I (IGF-I) system. Although the precise role of IGF-I in the context of ovarian physiology remains to be determined, it is likely that IGF-I may engage in the amplification of gonadotrophin hormonal action. These facts and experiments with animals establishing the ovaries of multiple species as a site of growth hormone (GH) reception and action have led to the use of recombinant GH (rGH) as an adjunctive agent to potentiate ovulation induction by exogenous gonadotrophins. Whether intraovarian IGF-I plays an intermediary role in GH hormonal action at the ovarian level remains uncertain at present. The aim of this study was to evaluate whether rGH administration to pre-menopausal women could modify the expression of the IGF-I gene in the ovary. The expression of the IGF-I gene was examined in a time-dependent manner in normal pre-menopausal ovaries obtained from nine women treated with rGH and nine control women treated with placebo, using solution hybridization/RNase protection assays. Ovarian tissue samples were obtained 24 h (six women) and 7 days (12 women) following rGH/placebo injection. Total RNA (20 microg) from whole pre-menopausal ovaries (with or without rGH treatment) as well as from human granulosa cells was hybridized with a human IGF-I antisense RNA. IGF-I peptide, but not oestradiol, serum concentrations increased significantly 24 h after rGH injection. IGF-I gene, however, was not expressed in the luteinized granulosa cells and whole pre-menopausal ovaries irrespectively of rGH treatment in ovarian samples analysed both 1 and 7 days following rGH injection. On the contrary, IGF-II mRNA transcribed from the fetal or fetal-neonatal IGF-II promoter and IGF-I receptor mRNA (both used as hybridization control) were both found in whole pre-menopausal ovary and luteinized granulosa cells. Nevertheless, no changes in the hybridization patterns were seen in the absence or presence of rGH. These studies demonstrate that rGH administration to normal premenopausal women does not change the expression of insulin-like growth factors and their receptor genes in the pre-menopausal human ovary. Furthermore, these results provide further evidence against locally produced IGF-I as responsible for any ovarian effects seen in systemic rGH administration.

Adult↗

Influence of weight and gonadal status on total and regional bone mineral content and on weight-bearing and non-weight-bearing bones, measured by dual-energy X-ray absosorptiometry.

OBJECTIVE: To evaluate the influence of weight on total body bone mineral content (BMCTB) and regional body bone mineral content (head, arms, trunk and legs). This was studied in accordance with gonadal status and the weight-bearing or non-weight-bearing status of each region. METHODS: The study included 94 postmenopausal women (mean age 60.6 +/- 10.5 years), 36 perimenopausal women (mean age 49.0 +/- 2.3 years) and 60 premenopausal women (mean age 36.1 +/- 6.9 years). Full-body bone densitometry (DXA), for measuring total body bone and regional bone mineral content, was carried out in all the women. RESULTS: Among these groups, the influence of 1 kg of body weight on total and regional bone mineral content (percent) did not differ (paired test P ns). In the overall group of women, paired comparison showed differences between the head and other zones measured (P = 0.036-0.004). In the overall group of women, no differences were found in the percent influence of 1 kg body weight on bone mineral content in any study zone (by ANOVA, Fisher's PLSD post hoc test and the Kruskal-Wallis test). In the overall group of women, Fisher's r to z test revealed a non-significant relationship between weight and the bone mineral content of the head (r = 0.49, P ns) but in every other region the relationship between weight and bone mineral content was significant (r = 0.36-0.54, P < 0.0001 in all). CONCLUSIONS: The effect of body weight on BMCTB and regional did not differ significantly with either gonadal status or weight-bearing (legs) and non-weight-bearing bones (arms).

Absorptiometry, Photon↗

Correlation of ultrasound bone velocity with dual-energy X-ray bone absorptiometry in rat bone specimens.

RATIONALE AND OBJECTIVES: To investigate bone mass measurements by ultrasound bond velocity (UBV) in bone specimens obtained from experimental animals. METHODS: The authors made UBV measurements in 40 femurs and tibias dissected from Sprague-Dawley rats (14 weeks-old, mean weight 290 g) and compared them with bone densitometric measurements made on the same material using dual-energy x-ray absorptiometry (DXA). RESULTS: The coefficient of variation for UBV measurements, based on values obtained in five femurs and five tibias at different times, was 0.2% and 0.3% respectively. Regression studies yielded a correlation between UBV and bone mineral density in femur of r = 0.87 (P < 0.0001) and with bone mineral content of r = 0.65 (P < 0.0001); in the tibia similar levels of significance were obtained. The correlation between femur weight and UBV was r = 0.51 (P < 0.0005) and with bone mineral content it was r = 0.79 (P < 0.0001). Partial correlation between UBV and femur bone mineral density, with respect to bone weight, was r = 0.68 (P < 0.001), and with femur bone mineral content was r = 0.71 (P < 0.0001). In the tibia measurements were similarly significant. CONCLUSIONS: Measurements of bone mass made with ultrasound transmission velocity are precise correlate well with DXA measurements.

Absorptiometry, Photon↗

Behavior of bone mass measurements. Dual energy x-ray absorptiometry total body bone mineral content, ultrasound bone velocity, and computed metacarpal radiogrammetry, with age, gonadal status, and weight in healthy women.

RATIONALE AND OBJECTIVES: Bone mass as measured by dual energy x-ray absorptiometry varies with body weight. The authors studied the behavior of bone mass measurements made by ultrasound bone velocity and metacarpal radiogrammetry in relation to body weight. METHODS: Eighty healthy women were studied: 40 post-menopausal and 40 premenopausal (mean age 60 +/- 6 and 38 +/- 8 years, respectively). The authors performed in every subject the following studies: a radiograph of the nondominant hand for metacarpal cortical thickness, a study of the 2nd to 5th proximal phalanges for ultrasound bone velocity, and total bone mineral content by dual energy x-ray absorptiometry. RESULTS: The measurements obtained with the three methods correlated significantly with each other (P < 0.0001). The only parameter related significantly with weight were total bone mineral content (P < 0.0001). In the premenopausal women, age did not correlate with any measurement. In the postmenopausal women, age correlated significantly with the three measured parameters (P < 0.0058 to P < 0.0001). CONCLUSIONS: Weight did not influence ultrasound bone velocity and metacarpal cortical thickness measurements.

Absorptiometry, Photon↗

Regulation of the genes for insulin-like growth factor (IGF) I and II and their receptors by steroids and gonadotropins in the ovary.

Insulin-like growth factors (IGFs) I and II are two single-chain polypeptide hormones that are structurally related to each other and to proinsulin. Among the large number of growth factors involved in ovarian physiology, IGF-I and IGF-II are considered to be important progression factors for ovarian follicular development. To explore the ovarian expression of IGF-I, IGF-II and their receptor genes, a solution hybridization/RNase protection assay, was used. IGF-I mRNA was seen in the granulosa cells, and IGF-II mRNA in the theca-interstitial compartment. To study the hormonal regulation of the IGF-I and IGF-II gene, immature (21-day-old) hypohysectomized rats were treated with FSH (10 micrograms/day), GH (150 micrograms/day) and diethylstilbestrol (DES subcutaneous implant/5 days). Estrogen differentially regulated ovarian IGF-I and IGF-II gene expression. In concert with GH, estrogen up-regulated ovarian IGF-I mRNA, but significantly decreased hepatic IGF-I gene expression. Both IGF receptors (type I and type II) as well as the insulin receptor gene, were expressed in both ovarian cells. The expression of the type I IGF receptor gene (but not the type II IGF gene) was up-regulated by FSH and estrogen in vivo. In conclusion, these studies may serve to better understand the auto paracrine role of IGF, and their receptors in the pathophysiology of follicle recruitment, oocyte maturation and potentially embryo development.

Animals↗

Biochemical markers of nutrition in osteoporosis.

Thirty-six women with vertebral osteoporosis showed significantly decreased levels of biochemical markers of nutrition, transferrin (P < 0.001), prealbumin (P < 0.001), retinol binding-protein (P < 0.001), and fibronectin (P < 0.001), compared with 40 healthy women of similar age. Multiple regression analysis showed a significant (R2 = 0.509; P = 0.0068) correlation between bone mineral content and biochemical markers of nutrition in the osteoporotic patients but not in the control group. These data suggest that postmenopausal osteoporosis may be associated with a nutritional deficiency.

Aged↗

The relationship of total body bone mineral (TBBMC) to anthropometric variables in postmenopausal women, and contribution of chronological age and years since menopause to TBBMC loss.

Dual energy X-ray absorptiometry measurements of total body bone mineral content (TBBMC), fat body mass (FBM) and fat mass percentage (%FM), lean body mass (LBM) and body weight (BW) were performed on 168 normal postmenopausal females. They were matched regarding life style and habits and had body mass index under 30. Their TBBMCs were correlated with these measurements, with chronological age (CA) and with the number of years since menopause (YSM). There was no correlation between TBBMC and %FM and LBM, but there was with BW (p < 0.001). There was a significant and negative correlation (r = -0.453, p < 0.001) between TBBMC and CA and to a higher range (r = -0.697, p < 0.001) with YSM. Menopausal females over 60 (n = 87) presented less bone mass than younger females (n = 81) (p < 0.01). These data suggest that regarding TBBMC, menopausal onset is a more important factor in bone mass loss, which persists rather markedly even during periods of time far from menopause and that TBBMC depends more on BW than on LBM and FM in women.

Adipose Tissue↗

Insulin-like growth factor I gene expression by primary cultures of ovarian cells: insulin and dexamethasone dependence.

A growing body of information now supports the existence of a complete intraovarian insulin-like growth Factor I (IGF-I) system replete with ligands, receptors, and binding protein(s). However, studies concerned with the regulation of ovarian IGF-I gene expression remain scarce. It was thus the objective of this communication to evaluate the expression of the IGF-I gene in the immature rat ovary under in vitro conditions. Whole ovarian dispersates or isolated granulosa cells were cultured for up to 96 h under serum-free conditions in the absence or presence of the indicated experimental agents. Extracted total RNA was subjected to a sensitive solution hybridization/RNase protection assay using 32P-labeled rat IGF-I and/or type I IGF receptor antisense RNA probes. Cultured in the absence or presence of FSH (100 ng/ml), whole ovarian dispersates (or isolated granulosa cells) displayed time-dependent (FSH-independent) decrements in the relative abundance of IGF-I transcripts apparent as early as 3 h after the onset of culture. No evidence of recovery was apparent by 96 h of culture. The apparent lack of an FSH effect did not reflect diminished biopotency as attested to by the ability of the hormone to promote time-dependent increments in the accumulation of progesterone. Importantly, the apparent decrease in ovarian IGF-I gene expression proved to be IGF-I specific in that type I IGF receptor transcripts displayed a substantial and sustained (for up to 96 h) FSH-independent increase beginning at the 24-h time point. At no point were IGF-II transcripts detected. The apparent decrease in the expression of IGF-I did not reflect the lack of extracellular matrix support in that neither laminin, collagen, nor whole serum supported sustained ovarian IGF-I gene expression. Treatment of whole ovarian dispersates with pharmacological concentrations of either insulin (1 micrograms/ml) or dexamethasone (10(-7) M) did not reverse the decline in IGF-I gene expression. Importantly, however, the combined application of both insulin and dexamethasone resulted in virtually complete preservation of IGF-I gene expression, the relative abundance of the corresponding transcripts proving uniform throughout. Taken together, these in vitro observations reveal irreversible (FSH-independent) decrements in ovarian IGF-I (but not type I IGF receptor) gene expression, the preservation of which required the concurrent provision of both insulin and dexamethasone.

Animals↗

Crush fracture syndrome in senile osteoporosis: a nutritional consequence?

Osteoporosis is a very important age-related health problem. The body's composition changes with age, and these changes are a true reflection of aging and of the individuals's nutritional status. Mineral content changes have been reported in vertebral osteoporosis. Interestingly, enough, there have not been reports on concomitant water, fat, and fat-free mass changes associated with this condition. In this report, changes in the latter parameters are compared between patients with osteoporosis and controls. The four components (water, mineral, fat, and fat-free mass) were found significantly reduced (p less than 0.001) in osteoporosis. Serum albumin and protein mass were also reduced (p less than 0.001).

Aged↗

Sex differences in the acquisition of total bone mineral mass peak assessed through dual-energy X-ray absorptiometry.

Dual energy X-ray absorptiometry evaluation of total body bone mineral content (TBBM), total bone mineral density (TBMD), and regional bone mineral content (BMC) (head, trunk, arms, and legs) was carried out in order to assess sex differences of bone in 120 women and 121 men aged 15-29 years. Subjects from both sexes were divided into 5-year groups (15 through 19, 20 through 24, and 25 through 29 years old, respectively). Significantly higher values for TBBM, TBMD, and regional BMC were observed in males compared with females in the 20 to 24 and 25 to 29-year-old groups (P less than 0.001), but not in the group aged 15-19. After adjusting TBBM for lean body mass (LBM), we observed significantly lower values of TBBM/LBM in the males compared with females in all the age groups. A positive and significant correlation was observed between TBBM and age in the males of all the groups (r = 0.624, P less than 0.001), but not in the females. These data suggest that total bone mass peak acquisition takes place earlier in women than in men, leading to more reduced bone mass value, which in turn may be an osteoporosis predisposing factor.

Absorptiometry, Photon↗

Salmon calcitonin reduces vertebral fracture rate in postmenopausal crush fracture syndrome.

The effectiveness of calcitonin on the vertebral fracture rate in postmenopausal osteoporosis was assessed through the skeletal deformity index (SDI) and the new vertebral fracture rate per 100 patient-years in a group of 32 women with postmenopausal osteoporosis treated by us with 100 IU of salmon calcitonin and 500 mg of elemental calcium for 10 consecutive days each month, and in another group of 28 women with postmenopausal osteoporosis treated with 500 mg of elemental calcium only for 10 consecutive days each month. Both groups were age-matched. The follow-up was a retrospective randomized study over 24 months. Thirty of the 32 women of the calcitonin group and 27 of 28 women of the calcium group finished treatment. The SDI was stabilized after six months in the calcitonin group (0.57 +/- 0.13, 0.62 +/- 0.18, 0.63 +/- 0.16 and 0.64 +/- 0.17, at base line, 6, 12 and 24 months respectively). The calcium group showed a significant increase only at 12 months (P less than 0.01) and 24 months (P less than 0.05) (0.61 +/- 0.16, 0.63 +/- 0.16, 0.69 +/- 0.16, and 0.73 +/- 0.15, at base line, 6, 12 and 24 months respectively). At 24 months, the new vertebral fracture rate decreased by 60% (20%, 14% and 8% at 6, 12 and 24 months respectively) in the calcitonin group and increased by 35% (31%, 33% and 42%, at 6, 12 and 24 months respectively) in the calcium group (P less than 0.025). These results show that calcitonin induced a significant reduction in postmenopausal osteoporotic vertebral fractures.

Aged↗

Total and regional bone mineral content in relation to menopause.

Total body bone mineral content (TBBM) and anatomical region bone mineral content (head, trunk and extremities) were measured using dual-energy X-ray absorptiometry in 188 women aged 60 +/- 6 years, of whom 154 were normal and 34 were osteoporotic. Of the 154 normal subjects, 90 were premenopausal (40 aged 44 +/- 3 years and 50 aged 34 +/- 8 years), the remaining 64 being postmenopausal and aged 58 +/- 7 years. There were no TBBM or regional changes in the premenopausal women, whereas there was a significant reduction in bone mineral content in the postmenopausal as compared with the premenopausal women in all regions. The osteoporotic subjects showed a general decrease (P < 0.001) in all measurements which was more marked in the trunk. The rate of TBBM reduction was 16% in the normal postmenopausal women and 29% in the osteoporotic subjects. All the postmenopausal women (both normal and osteoporotic) showed lower TBBM values than those in the Wisconsin trial, similar results being obtained in the case of the premenopausal group. Such differences can only be explained by hardship experienced by these now postmenopausal women during their childhood and adolescence.

Absorptiometry, Photon↗

Human intraovarian interleukin-1 (IL-1) system: highly compartmentalized and hormonally dependent regulation of the genes encoding IL-1, its receptor, and its receptor antagonist.

To delineate the scope of the human intraovarian IL-1 system we used a solution hybridization/RNase protection assay to test for expression of the genes encoding IL-1, its type I receptor (IL-1R), and its receptor antagonist (IL-1RA). IL-1 transcripts were not detected in whole ovarian material from days 4 or 12 of an unstimulated menstrual cycle but transcripts (IL-1 beta much greater than IL-11 alpha) were detected in preovulatory follicular aspirates from gonadotropin-stimulated cycles. Concurrently obtained peripheral monocytes did not contain IL-1 beta transcripts but macrophage-depleted follicular aspirates did, thus implicating the granulosa cells as the site of IL-1 expression. IL-1R transcripts were detected in RNA from whole ovaries and follicular aspirates but not in RNA from peripheral monocytes. IL-1RA transcripts were detected in whole ovarian material as well as in macrophage-free follicular aspirates. Cultured human granulosa and theca cells did not contain mRNA for IL-1 beta or IL-1RA but did contain mRNA for IL-1R. Treatment of cell cultures with forskolin (25 microM) induced IL-1 beta transcripts in granulosa but not theca cells. Forskolin also increased the basal levels of IL-1R transcripts in both granulosa and theca cells but did not induce IL-RA transcripts in either cell type. Taken together, these findings reveal the existence of a complete, highly compartmentalized, hormonally dependent intraovarian IL-1 system replete with ligands, receptor, and receptor antagonist.

Adult↗

Granulosa cell-derived insulin-like growth factor (IGF) binding proteins are inhibitory to IGF-I hormonal action. Evidence derived from the use of a truncated IGF-I analogue.

An increasing body of information now suggests that insulin-like growth factor (IGF) binding proteins (BPs) may serve as antigonadotropins at the level of the ovary. It is the objective of the present communication to evaluate the functional role of endogenous (granulosa cell-derived) IGFBPs by exploiting the unique properties of des(1-3)IGF-I, a naturally occurring IGF-I analogue characterized as a weak ligand of IGFBPs but not of type I IGF receptors. Given IGFBP-replete circumstances, des(1-3)IGF-I proved more potent (10-fold) than its intact counterpart in promoting the follicle stimulating hormone (FSH)-stimulated accumulation of progesterone by cultured rat granulosa cells. In contrast, des(1-3)IGF-I proved virtually equipotent to the unmodified principle under IGFBP-deplete circumstances. Taken together, these findings are in keeping with the notion and that the apparently enhanced potency of des(1-3)IGF-I (under IGFBP-replete conditions) is due to its diminished affinity for endogenously generated IGFBPs and that rat granulosa cell-derived IGFBPs are inhibitory to IGF (and thus inevitably to gonadotropin) hormonal action. Accordingly, the reported ability of gonadotropins to attenuate IGFBP release by granulosa cells may be designed to enhance the bioavailability of endogenously generated IGFs in the best interest of ovarian steroidogenesis.

Animals↗

Effect of testosterone on insulin-like growth factor-I (IGF-I) and IGF-I receptor gene expression in the hypophysectomized rat.

Circulating levels of insulin-like growth factor-I (IGF-I) increase during puberty, concurrent with an increase in the levels of GH and the gonadal steroids. The relationship between the changes observed in IGF-I and testosterone (T) levels are not understood. This study was designed to determine whether T has a direct effect on IGF-I serum levels, liver IGF-I gene expression, and epiphyseal growth plate IGF-I and IGF-I receptor gene expression. Hypophysectomized castrated rats were divided into four groups of six animals. The T group was treated with sc T for 5 days. The GH group was treated with a single dose of GH. The GH plus T group was treated with T for 5 days and with GH on the last day of treatment. The control group was injected for 5 days with vehicle alone. Serum IGF-I levels in the T group were not significantly different from those in the control group, and the levels in the GH plus T group were not significantly different from those in the GH group. There was an 11-fold increase in liver IGF-I mRNA abundance in the GH group compared to the control group (P less than 0.01). Liver IGF-I mRNA levels in the T group were not significantly different from those in the control group. When liver IGF-I mRNA levels in the GH plus T group were compared to those in the GH-treated group, no significant differences were found. In the epiphyseal growth plate region, there was a 12-fold increase in IGF-I mRNA levels in the GH group compared to those in the control group, but there was no statistical difference between the control and T groups. IGF-I mRNA levels in the GH plus T group were not significantly different from those in the GH-treated group. IGF-I receptor mRNA abundance was not significantly different in the T group compared to that in the control group. GH decreased IGF-I receptor mRNA by 2.3-fold, but T treatment before GH injection did not change this effect. We conclude that in castrated hypophysectomized rats, T does not stimulate IGF-I gene expression in the liver, nor does it increase IGF-I serum levels. T alone also does not have a stimulatory effect on IGF-I or IGF-I receptor gene expression in the epiphyseal growth plate region.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗