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Biomedical subjects

M Roger

Publications and source records attributed to M Roger.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Treatment of central precocious puberty with sustained-release triptorelin].

Central precocious puberty is defined as the appearance of morphological and biological changes induced by the early maturation of the hypothalamic-pituitary-gonadal system before eight years of age in girls and ten years of age in boys. This early onset of the gonadotropin-releasing hormone pulse generator activation leads to secretion of gonadal steroids and therefore to the development of secondary sexual characteristics. The aim of medical treatment is to suppress the secretion of sex hormones. A dramatic improvement has been achieved with the development of gonadotropin releasing hormone agonists which induce a reversible suppression of gonadotropin secretion. Since 1986, triptorelin (Decapeptyl) (D-Trp6-LHRH) has been available for this indication as a sustained-release formulation allowing an intramuscular injection of 3.75 mg every 4 weeks. Results published up to now concern 352 children (325 girls and 27 boys). The pituitary-gonadal suppressive effect has been confirmed. The complete suppression of gonadal secretions induced a rapid regression of secondary sexual characteristics as early as the 3rd month of therapy, and decreased the growth rate acceleration which normalizes during the 3rd year of therapy. The progression of bone maturation clearly slowed down at the end of the first year of treatment so the final height prognosis significantly improved. Whatever length of the treatment period, the reversibility of the suppressive effect of triptorelin has been demonstrated. Puberty resumed 3 to 9 months after stopping the treatment. Tolerance of the medication was excellent. The rare side effects were minor and never led to treatment discontinuation: headaches (8% of the cases), hot flushes (12% of the cases). The percentage of drop out was very low.

Delayed-Action Preparations↗
PubMed1993

Profiles of plasma estrogens, progesterone and their metabolites after oral or vaginal administration of estradiol or progesterone.

Doses of 100 mg of micronized progesterone (P) and of 0.5 mg of micronized estradiol (E2) were administered vaginally and orally, respectively, in the early follicular phase of the menstrual cycle in six premenopausal women. In the second cycle, the same doses were administered in the same subjects, orally for P and vaginally for E2. Serial blood samples were collected and the following steroids were assayed by highly reliable techniques: P, E2, estrone (E1), deoxycorticosterone (DOC), 5 alpha- and 5 beta-pregnanolone and the sulfates of E1, E2, and DOC. Circulating P and E2 levels were higher after vaginal than after oral administration, while those of E1 were similar after either route. Metabolites of P (DOC, DOCS and pregnanolone) were higher after oral administration. Concerning estrogen sulfates, E1S concentrations were similar whichever the route, while those of E2S were lower after oral than after vaginal administration. This study has confirmed that metabolism of ingested P and E2 occurs mainly in the intestine. Moreover, P was predominantly metabolized to 5 alpha-reduced derivatives, whatever the route of administration. In view of the metabolic pathways which are operative and of the peripheral plasma levels which were found, the vaginal route appears to be more adequate than the oral one for hormone replacement therapy.

Administration, Intravaginal↗
PubMed1993

Inhibin and follicle-stimulating hormone levels in gonadotroph adenomas: evidence of a positive correlation with tumour volume in men.

OBJECTIVE: Gonadotroph adenomas are generally revealed by symptoms of mass effect at the stage of macroadenoma. Most of them hypersecrete FSH and/or gonadotrophin subunits. Rarely they hypersecrete LH, which could induce endocrinological symptoms. As the glycoprotein inhibin is secreted by the gonads under FSH control, we have evaluated whether high immunoreactive inhibin (iINH) levels correlated with FSH hypersecretion and whether iINH and FSH levels were related to tumour volume in subjects with gonadotroph adenomas. PATIENTS: Forty-five patients (30 men, 15 women) were retrospectively selected on the basis of immunostaining technique using specific antibodies raised against FSH-beta, LH-beta and glycoprotein alpha-subunit. MEASUREMENTS: Immunoreactive inhibin (iINH) was measured by radioimmunoassay using antiserum 1989 raised to bovine inhibin. Tumour volume index was the product in cm3 of length, width and height of the adenoma as assessed by computerized tomography. RESULTS: In men (age 21-61 years), iINH levels were positively correlated with FSH levels (Spearman's r = 0.67, P < 0.001), and both iINH and FSH levels were significantly correlated with tumour volume index (Spearman's r = 0.38, P < 0.05 and r = 0.39, P < 0.05 respectively). In the subgroup of men with normal FSH levels (n = 17), the correlation of FSH with tumour volume index was high: Spearman's r = 0.56, P < 0.05. In the post-menopausal women (n = 8, age > 55 years), iINH levels were undetectable or below the follicular phase range regardless of FSH values. In the premenopausal women (n = 7, age 22-49 years, follicular phase or amenorrhoea) iINH levels were above follicular phase range in three women including one who had very high FSH levels. CONCLUSIONS: These data show that in men with gonadotroph adenoma FSH levels are related to tumour mass and suggest that a significant part of circulating FSH in patients with normal FSH levels arises from the tumour. The significant correlation between iINH and FSH levels demonstrates that tumoral FSH is bioactive and that high iINH levels do not exert any feedback control on tumoral FSH secretion. Therefore the coexistence of high FSH levels with high iINH levels is strongly suggestive of a gonadotroph adenoma. Gonadotroph adenomas seem to represent a unique model of long-term FSH stimulation of inhibin-producing cells, in some way analogous to that created by repetitive administration of exogenous FSH.

Adenoma↗
PubMed1993

Impaired response of free alpha-subunits after luteinizing hormone-releasing hormone and thyrotropin-releasing hormone stimulations in beta-thalassemia major.

In order to clarify whether the damage in gonadotropin secretion due to iron overload in patients with beta-thalassemia is of pituitary or hypothalamic origin, 14 euthyroid patients (8 females and 6 males, age 15-24 years) affected by beta-thalassemia major with hypogonadotropic hypogonadism were studied. Luteinizing-hormone (LH), follicle-stimulating hormone (FSH) and free alpha-subunit (FAS) were measured during LH-releasing hormone (LH-RH) stimulation test, and thyroid-stimulating hormone (TSH), prolactin (PRL) and FAS during thyrotropin-releasing hormone (TRH) stimulation test. During LH-RH stimulation, the mean basal LH, FSH and FAS levels were similar to those found in normal prepubertal children, but the peak values were lower than those found in such children. Also during TRH stimulation, the mean peak values of FAS were lower than those of normal prepubertal children, but the TSH response was normal. The lack of response of gonadotropins and FAS to LH-RH cannot exclude hypothalamic failure; however, the normal response of TSH to TRH, in spite of the poor response of FAS, indicates that the origin of hypogonadotropic hypogonadism is the pituitary damage concerning not only the gonadotroph but also the thyrotroph cells.

Adolescent↗
PubMed1993

Interrelation between plasma sex hormone-binding globulin and plasma insulin in healthy adult women: the telecom study.

In order to study the relationship between plasma sex-hormone-binding globulin (SHBG) and insulin levels in healthy women, we investigated the association between plasma SHBG and insulin in an occupational sample of 786 nonhormone-using women. Levels of plasma SHBG showed a stepwise decrease with increasing fasting plasma insulin in premenopausal as well as in postmenopausal women. In these cross-sectional data, this significant negative relationship between SHBG and insulin was shown to be independent of age, body mass index, subscapular skinfold, fasting and 2-h plasma glucose in both groups. The etiology and the consequences of this inverse association between SHBG and insulin are unclear. Prospective and clinical studies in women will be necessary to determine the direction and causal nature of the association between SHBG and insulin, as well as its mechanism and its physiological and/or pathophysiological consequences.

Adult↗
PubMed1993

Role of estradiol in the rise in follicle-stimulating hormone levels during the luteal-follicular transition.

Follicular recruitment takes place under FSH stimulation at the end of the luteal phase and the beginning of the subsequent follicular phase, the so-called luteal-follicular transition (LFT). Inhibin, a known suppressor of FSH, has been implicated in the onset of the rise in FSH levels, as the fall in its immunoreactive plasma levels after the demise of the corpus luteum has been shown to correlate negatively with the increase in FSH. To analyze the role of estradiol (E2), another inhibitor of FSH secretion in the LFT, we designed an experimental paradigm to dissociate the physiological falls in inhibin and E2. This was achieved by extending the duration of luteal plasma E2 levels with transdermal E2 treatment. Untreated ovulatory cycles in seven healthy female volunteers, aged 28-38 yr, were compared with E2-treated cycles in the same subjects, with treatment starting on the 10th day after the LH surge and continuing through the 4th day of the following menses [either 0.2 mg (n = 6; G1) or 0.1 mg (n = 6; G2) E2 daily]. Blood samples were obtained daily from the LH surge until the 11th day of the next cycle. Immunoreactive plasma inhibin levels reached a nadir on day 2 of menses regardless of whether women received E2. Plasma E2 (mean +/- SEM) levels remained within the normal luteal range (220 +/- 51 to 635 +/- 279 pmol/L) until the end of the treatment period in G2 (range, 253 +/- 40 to 382 +/- 62 pmol/L), but not in G1 (range, 598 +/- 195 to 1835 +/- 1259 pmol/L). However, the onset of the FSH rise was clearly delayed, from a mean of 2 days before menstruation in the controls to day 4 of the cycle in G1 and G2. Peak plasma FSH levels were attained within 6 days in the controls and within 2 or 3 days in both treatment periods. Our data suggest that it is the decrease in plasma E2 rather than inhibin that is the triggering signal for the LFT rise in plasma FSH. The exact roles of inhibin and other gonadal proteins (e.g. activins) in follicular recruitment remain to be determined.

Adult↗
PubMed1993

Anti-müllerian hormone and testosterone serum levels are inversely during normal and precocious pubertal development.

Anti-Müllerian hormone (AMH), also called Müllerian inhibiting substance or factor, is produced by Sertoli cells from fetal life until puberty. In the present study, AMH, testosterone (T), LH, and FSH were measured by immunochemical methods in the serum of 50 boys with normal or delayed pubertal development, 4 patients with suspected androgen insensitivity, and 11 patients with either central (CPP) or gonadotropin-independent (GIPP) precocious puberty to investigate the hormonal regulatory mechanisms of AMH secretion at puberty. An inverse relationship between AMH and T levels was demonstrated. In boys with normal or delayed puberty with T concentrations below 6.7 nmol/L, AMH values were elevated (mean +/- SEM, 22.4 +/- 3.1 micrograms/L) and widely dispersed. In subjects with T levels over 6.7 nmol/L, AMH levels were uniformly low (3.4 +/- 0.5 micrograms/L), except in patients with suspected androgen insensitivity. No significant relationship was found between AMH and gonadotropin levels. Similar results were obtained in patients with either CPP or GIPP. Longitudinal studies were performed on four boys with CPP and two with GIPP before and after treatment. At the time of diagnosis, the T concentration was high, and AMH levels were usually low in CPP and GIPP patients alike. When appropriate treatment was initiated, the T concentration was normalized within 2-4 weeks, but restoration of prepubertal AMH levels required several months. Mature Sertoli cells were observed in testicular biopsies performed in three patients with untreated GIPP. Our results suggest that gonadotropins are not directly implicated in repression of AMH synthesis at puberty, but, rather, that the decrease in AMH production is the consequence of an androgen-mediated, long term, reversible chain of events leading to morphological and functional maturation of the Sertoli cells. Thus, the fall in serum AMH levels appears to be an excellent marker of Sertoli cell pubertal development.

Adolescent↗
PubMed1993

[The corticorubral projection in rats: topographic distribution of fibers arising from areas of the sensorimotor cortex functionally identified by microstimulation].

The combination of microstimulation and anterograde tracing techniques reveals that different regions of the sensorimotor cortex project to different sectors of the red nucleus (NR). V-FEF projects to the dorsolateral sector, JLT to the dorsal sector, RFL and CFL to the dorsomedial and medial sectors, respectively, and HL to the ventral and ventrolateral sectors. Moreover, the NR receives fibers from the 2 somatosensory cortical areas examined in this study. The vibrissae area projects to the dorsolateral sector and the hand area to the dorsomedial sector.

Animals↗
PubMed1993

Relationship between gonadotrophins, inhibin and sex steroid secretion during the periovulatory period and the luteal phase in the blue fox (Alopex lagopus).

The blue fox is a monestrous seasonal breeder with a pro-oestrus and oestrus lasting several days and a prolonged luteal phase in non-pregnant as well as pregnant vixens. Ovulation occurs 2 days after the preovulatory luteinizing hormone (LH) peak at the onset of oestrus; oocytes are ovulated as primary oocytes and maturation is completed 2-3 days later. Fertilization is possible during all stages of oocyte maturation until degeneration of oocytes 5 or 6 days after the LH peak. In this study, changes in plasma concentrations of follicle-stimulating hormone (FSH) and immunoreactive inhibin (iINH) and their relationships with LH, oestradiol, androstenedione, testosterone and progesterone secretion and with the periovulatory events, were determined throughout the reproductive cycle of 14 vixens. In late anoestrus and pro-oestrus, FSH and iINH were inversely related to each other (r = -0.84, P < 0.001); whereas FSH concentrations declined to reach low values within the 5 days preceding the LH peak, iINH secretion increased, as did that of oestradiol and androgens. Thereafter, iINH and steroid concentrations with the exception of progesterone reached maximal values at the time of the LH and FSH peaks and decreased within the following 2-3 days in the early luteal phase. Progesterone started to increase simultaneously with the LH peak, and when oocyte maturation was completed (around day 4), progesterone concentrations were increasing, while those of other hormones were low. A postovulatory release of FSH was detected between days 6 and 10; it preceded the rise in iINH, which began on day 8 when concentrations of progesterone were already high and those of oestradiol and LH were low. Progesterone and iINH were positively correlated over the period day 6 to day 49 (r = 0.62, P < 0.01). These results indicate that, in the blue fox, iINH is secreted by the preovulatory follicle and the corpus luteum; that during pro-oestrus, iINH may act in synergy with oestradiol to reduce the secretion of FSH and that after the LH peak the decrease of iINH and oestradiol concentrations may be responsible for the postovulatory release of FSH, which in turn causes an increase in iINH, possibly secreted by the corpus luteum and, as a result, FSH secretion is suppressed.

Androstenedione↗
PubMed1993

[Late diagnoses of 21-hydroxylase deficiencies in children (after the age of 3 years].

To evaluate the heterogeneity of 21-hydroxylase deficiency with delayed symptoms, clinical and laboratory findings at presentation in 29 patients whose first symptoms occurred after three years of age were analyzed retrospectively. In 12 patients, these data were confronted with the results of molecular CYP21B gene analysis. Age at onset was 7 years on average and was comparable in boys and girls. Premature puberty was the most common presenting symptom [n = 24], whereas hirsutism, clitoral enlargement, and menstruation disorders were less frequent. Six cases were diagnosed as the result of routine studies of family members of index patients. The bone age over statural age ratio was greater than 1 in 19 of the 27 patients. Baseline 17-OH-progesterone levels were elevated in 22 of the 27 patients; magnitude of the elevation varied widely. Levels of 17-OH-progesterone after stimulation with immediate-action tetracosactide were closely correlated with baseline values and established the diagnosis in doubtful cases. Four patients had post-stimulation 17-OH-progesterone levels under 10 ng/ml, suggesting that were heterozygous for the disease. An important finding was that the magnitude of the devation in 17-OH-progesterone was not clearly correlated with clinical findings at presentation (age at onset, growth rate, advance in bone age). Molecular CYP21B gene analysis performed in 12 patients disclosed a homozygous 281 Val Leu mutation in 6 cases. This is the most commonly reported mutation in delayed onset forms. Two patients were heterozygous for the 281 Val Leu mutation and had an allele associated with severe disease, suggesting that the least severely affected chromosome governed clinical presentation of the disease. One boy had an allele associated with neonatal onset on both chromosomes; molecular analysis indicated a risk of antenatal masculinization of female fetuses in this family. This study showed that delayed onset 21-hydroxylase deficiency is a heterogeneous entity and that molecular analysis is essential to genetic counseling.

17-alpha-Hydroxyprogesterone↗
PubMed1992

The influence of aging on plasma sex hormones in men: the Telecom Study.

From April 1985 to July 1987, 1,408 healthy white men aged 20-60 years in Paris, France, recruited on an occupational basis, underwent a physical examination and measurements of plasma sex hormones in a cross-sectional study. Both total testosterone and estradiol showed a significant stepwise decrease with age (p less than 0.001) starting in the early adult years, while estrone did not vary. These relations of testosterone and estradiol with age remained significant after adjustment for body mass index, subscapular skinfold, and tobacco and alcohol consumptions, and they were not modified by exclusion of the men who reported chronic disease. Both the mechanism for the early decrease in testosterone and its clinical significance merit further investigation.

Adult↗
PubMed1992

Interrelation between plasma testosterone and plasma insulin in healthy adult men: the Telecom Study.

Plasma insulin is a risk factor for diabetes mellitus and cardiovascular disease in men. We investigated the association between plasma testosterone and plasma insulin in an occupational sample of 1292 healthy adult men. Total plasma testosterone decreased with each decade of age and insulin increased with each decade of age. In these cross-sectional data, this significant graded inverse association between testosterone and insulin was independent of age. The association was reduced but not explained by the addition of obesity and subscapular skinfold to the model. Adjustment for alcohol consumption, cigarette smoking and plasma glucose did not materially alter the association. These results are the reverse of the positive association of androgens with insulin in women and suggest alternative possible explanations for the effect of hyperinsulinaemia on cardiovascular disease risk. Prospective studies will be necessary to determine the direction and causal nature of this association.

Adult↗
PubMed1992

Topographical organization of the projections from physiologically identified areas of the motor cortex to the striatum in the rat.

The present study was undertaken to determine in the rat the topography of the neostriatal projections originating from the motor cortex. For that purpose, anterograde tracers (Phaseolus vulgaris leucoagglutinin: PHA-L; wheat germ agglutinin conjugated to horseradish peroxidase: WGA-HRP) were deposited in discrete cortical sites physiologically identified by microstimulation. Five major motor areas were considered in this study: the rostral (RFL) and caudal (CFL) forelimb areas, the hindlimb (HL) area, the vibrissae motor-frontal eye field (V-FEF) region and the jaw, lips and tongue (JLT) area (according to the nomenclature of Neafsey et al.). The results indicate that functionally different regions of the motor cortex project to different sectors of the caudate putamen (CPU). All 3 distinct limb areas RFL, CFL and HL project to the dorsolateral quarter of the CPU, V-FEF area projects to the dorsomedial quarter, whereas the JLT area projects to the ventrolateral quarter. The pattern of terminal labeling is relatively consistent, whatever the cortical area in which the tracer is deposited. This pattern is characterized by the presence of two or more labeled bands which are obliquely oriented along a ventrolateral-dorsomedial axis. Control experiments were also undertaken in which a retrograde tracer (WGA-HRP) was deposited in various neostriatal loci. The results are congruent with the findings of the anterograde study and further indicate that a given neostriatal sector receives projections from cytoarchitectonically different but functionally related regions of the neocortex. The somatotopic features of both motor and somatosensory corticostriatal projections appear to be in register. In addition, the striatal distribution of motor cortical fibers was compared in 6 experimental cases to the compartmental subdivision of the striatum in patches and matrix, following immunohistochemical localization of calbindin 28 kDa. The calbindin-immunoreactivity is extremely weak in the dorsolateral sector but is higher in the central and ventrolateral parts of the CPU. In these deep striatal regions receiving fibers from V-FEF, JLT and, to a lesser extent, from the limb areas, the cortical fibers are mostly directed to the matrix. The band-like organization of the projection from the motor cortex is correlated to the patch-matrix organization. The patches correspond to the bands of low density of terminal fibers and the matrix to the bands of high terminal density. The present results provide an anatomical basis to both electrophysiological and behavioral observations suggesting that functional distinctions can be established between subregions of the striatum.

Animals↗
PubMed1992

Features of insulin-resistance syndrome in men from French Caribbean Islands. The Telecom Study.

The prevalence of diabetes is known to be high in the West Indies, whereas CVD seems relatively rare. This apparently contradicts the existence of the insulin-resistance syndrome, a cluster of metabolic abnormalities supposedly favoring both diabetes and cardiovascular complications. To address the question of whether this contradiction could be accounted for by specific features of this syndrome, we compared 1505 Caucasian and 181 Afro-Caribbean men, all participants in the French Telecom Study. The Afro-Caribbeans were of the same age and had the same BMI as the Caucasians; they also had significantly higher subscapular skin-fold thickness and fasting insulin level, but similar BP and blood glucose level, and significantly lower plasma triglyceride level. Thus, although some features of the insulin-resistance syndrome were present (central adiposity and high insulin levels), none of the associated metabolic abnormalities were present. However, within the Afro-Caribbean group, subjects with plasma insulin concentrations above the median (> 52 pM) had higher mean BP and glucose and triglyceride levels compared with subjects with insulin concentrations < or = 52 pM (P < 0.001). After adjustment for age and BMI, these differences, though smaller, still were statistically significant. These findings confirm that higher insulin concentrations are associated with higher levels of potentially atherogenic and diabetogenic metabolic parameters. However, depending on ethnic origin, the mean levels of these parameters seem to be different, with the consequence that, even if they are elevated with increasing insulin levels, they may not reach values high enough to determine a substantial risk of disease.

Adult↗
PubMed1992

[Connections of the posterior region of the thalamus in rats].

Using retrograde and anterograde tracing methods we have studied in the posterior region of the thalamus of the rat the distribution of: (1) the terminal fields of the main afferents arising from somatosensory centers (dorsal column nuclei, interpolar trigeminal subnucleus, somatosensory cortex), motor centers (red nucleus, motor cortex) and multimodal structures (deep layers of the superior colliculus, zona incerta, cingular cortex) and of (2) the neurons giving rise to the main efferents towards the sensorimotor cortex, the red nucleus, the deep layers of the superior colliculus and the zone incerta. The overlap of the retrograde and anterograde labeling reveals a relatively homogeneous region. Considering however the cortical connections, three different subdivisions can be distinguished: a caudal pole completely devoid of cortical connections, a medial subdivision receiving cortical afferents from the sensorimotor and cingulate cortices and a rostral pole reciprocally connected with the sensorimotor cortex. Therefore the rostral pole would be the only part of this region which should be included in the thalamus.

Afferent Pathways↗