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Biomedical subjects

M Roger

Publications and source records attributed to M Roger.

At least 91 records · Page 5Linked to original sources

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↗

[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↗

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↗

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↗

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↗

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↗

[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↗

Transdermal estradiol substitution therapy for the induction of puberty in female hypogonadism.

Fifteen patients aged 14.5-27.3 years (mean +/- SE 18.8 +/- 0.9) with pubertal development failure underwent replacement therapy with estradiol (E2) using a transdermal therapeutic system (TTS). Fourteen of them were affected by hypogonadotropic hypogonadism (11 with thalassemia major, 3 with multiple pituitary hormone deficiency), the 15th patient had an asymmetric gonadal dysgenesis (karyotype 45, X 0/46, XY). Two sizes (5 and 10 cm2) of E2 TTS, delivering respectively 25 and 50 micrograms of E2 a day for 3 1/2 days, were used in this study. All patients were initially given the lower dose of 25 micrograms, twice weekly for 3 weeks each month; 6 months after starting therapy, 5-10 mg oral medroxyprogesterone acetate (MPA) daily was added during the third week. Later, the following sequence was used: 25 micrograms E2 TTS (twice weekly), on days 1 through 14, and 50 micrograms E2 TTS (twice weekly), on days 15 through 25 of each month. On days 15 through 25, 5 mg daily of MPA were administered orally. The period of treatment ranged from 0.5 to 3 years. Breast development was obtained in all cases. The vaginal maturation index rose. Ultrasonography showed an increase of uterine size and uterine shape became of pubertal type. Withdrawal bleeding occurred in all patients. Plasma E2 levels rose to normal levels, estrone (E1) levels increased slightly. No change in plasma SHBG levels was observed. Urinary E2, E1 and estriol rose to maximum levels the 3rd day after the application of each system. Neither systemic side effects nor adverse metabolic effects were observed except for an increased sensitivity to the platelet aggregating agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

Cortical and subcortical connections of the pars compacta of the anterior pretectal nucleus in the rat.

The efferent and afferent connections of the dorsal part of the anterior pretectal nucleus, pars compacta (APc), were studied experimentally in the rat by using neurotracers. A restricted number of structures supply afferents to the anterior pretectal nucleus: the visual cortex (areas 17, 18 and 18a), ventral lateral geniculate nucleus and superficial layers of the superior colliculus. Additional afferents have been demonstrated originating from the Darkschewitsch nucleus, periaqueductal gray, zona incerta and anterior cingulate cortex. Efferent fibers are distributed to a sector of the deep mesencephalic nucleus just dorsolateral to the red nucleus, the basilar pontine gray, posterior and olivary pretectal nuclei, superficial layers of the superior colliculus, lateral posterior thalamic nucleus, ventral lateral geniculate nucleus and zona incerta. These anatomical observations indicate that the pars compacta of the anterior pretectal nucleus is closely related to visual centers, suggesting an involvement of this nucleus in visually mediated behavior.

Afferent Pathways↗

Effects of gonadotrophin releasing hormone antagonist and agonist on the pulsatile release of gonadotrophins and alpha-subunit in postmenopausal women.

OBJECTIVE: The present study was designed to further assess the mechanism of action of GnRH and GnRH analogues. DESIGN AND PATIENTS: Both the Nal-Glu GnRH antagonist and the D-Trp6 GnRH agonist were administered sequentially to nine normal, post-menopausal women. MEASUREMENTS: A baseline study of pulsatile LH, FSH and free alpha-subunit secretion was performed, with sampling every 10 min for 8 h, and then repeated 8 h after a single subcutaneous injection of Nal-Glu GnRH antagonist (5 mg). Sampling was repeated 21 days after the intramuscular injection of a depot preparation of D-Trp6 GnRH (3.75 mg) in the same women. RESULTS: The baseline sampling period showed synchronous pulses of LH and free alpha-subunit. The antagonist Nal-Glu decreased plasma LH (71%) and free alpha-subunit (43%). However, with the single dose of 5 mg, pulsatile LH and free alpha-subunit release were not completely suppressed and remained temporally correlated. The GnRH agonist had a potent inhibitory action on plasma immunoreactive LH (IRMA) (93%). In contrast, it increased the mean plasma levels of free alpha-subunit from 1.66 +/- 0.01 to 5.06 +/- 0.02 micrograms/l (205%). The pulsatile secretory patterns of both LH and free alpha-subunit were abolished by the agonist. Immunoreactive FSH levels were decreased by the antagonist (24%) and suppressed by the agonist (93%). CONCLUSIONS: The pulsatile study confirms the different mechanism of action of GnRH analogues. Following antagonist administration, low amplitude free alpha-subunit pulses persist and are synchronous with residual LH pulses. In contrast, LH and free alpha-subunit are not maintained under agonist treatment. These data provide evidence for the differential regulation of LH and free alpha-subunit by GnRH.

Female↗

Long-term results of long-acting luteinizing-hormone-releasing hormone agonist in central precocious puberty.

Thirty children with precocious puberty (24 girls aged 6.5 +/- 2.3 years and 6 boys aged 7 +/- 2.9 years) were treated over 5 years with Decapeptyl. In girls, the menses disappeared, breast enlargement regressed, and uterus and ovary sizes returned to prepubertal values. In boys, a significant decrease of testicular size was observed. Plasma levels of estradiol and testosterone, and basal and post-luteinizing hormone (LH)-releasing hormone (LHRH) LH and follicle-stimulating hormone (FSH) remained in the prepubertal range. Growth velocity decreased after 1 year from 9.7 +/- 3.5 to 5.5 +/- 1.3 cm/year, while the height age/bone age ratio was normalized in both sexes after 3 years. In 15 girls, Decapeptyl was interrupted after 2.3 years. During those 2.3 years, bone age increased from 11.6 +/- 0.8 to 12.5 +/- 0.7 years with a growth velocity of 5.3 +/- 1.8 cm/year. During the year following interruption, height increased from 152.2 +/- 4.9 to 157.7 +/- 4.9 cm (growth velocity 5.5 cm/year) and bone age from 12.5 +/- 0.7 to 13.5 +/- 0.6 years. One year after treatment, plasma levels of estradiol were 106.7 +/- 84.7 pg/ml, of LH, 25.5 +/- 17.6 mIU/ml, and of FSH, 10.8 +/- 5.9 mIU/ml. Menses appeared in 13 girls. Moreover, 18 months after interruption, bone age was 13.9 +/- 0.6 years and height 159.5 +/- 5.2 cm, being significantly superior to the final height of a historical control group: 151.5 +/- 4.8 cm (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗

Etiologies of late puberty.

An expected lack of pubertal development can be due to an already diagnosed disease. The diagnosis of an unexpected lack of puberty is a difficult task. We have analyzed the etiologies of late puberty in 106 adolescents: 68 boys aged over 15 years and 38 phenotypic girls aged over 13 years. According to their clinical and biological (gonadotropin) data, they were classified in 3 groups. In the first group, hypergonadotropism was observed only in 19 females; pure gonadal dysgenesis was found in 2 cases with 46,XY, in 2 with 46,Xdel(Xq) karyotypes and 9 cases were 46,XX constitutions; 2 sisters had also blepharophimosis; in 3 cases the ovarian failure was due to autoimmune disease, and 1 case, genetically male, had 17 alpha-hydroxylase deficiency. The second group had gonadotropin insufficiency and consisted of 68 adolescents, 57 males and 11 females, with low gonadotropin levels: 33 were anosmic; in the boys, cryptorchism was present in 68% and micropenis in 31%; 38 had a familial history of hypogonadism, the transmission of which was matrilineal in 16, patrilineal in 13 and recessive autosomal in 7. The third group had low or low-normal gonadotropin levels: 22 cases of constitutional delay of puberty (11 cases in both sexes), demonstrated by further normal puberty during the follow-up. No clinical marker and familial history in 50% were noted.

Adolescent↗