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Biomedical subjects

P C Sizonenko

Publications and source records attributed to P C Sizonenko.

At least 37 records · Page 2Linked to original sources
PubMed1993

Evidence that neuropeptide Y could represent a neuroendocrine inhibitor of sexual maturation in unfavorable metabolic conditions in the rat.

Neuropeptide Y (NPY) is known to be involved in the central regulation of appetite, sexual behavior and reproductive function. Whereas central administration of NPY strongly stimulates feeding, diet restriction produces overexpression of NPY in the arcuate and paraventricular nuclei that might reflect behavioral adaptations to shortage of food. The role of NPY for the regulation of sexual function is still controversial. Whereas NPY is stimulatory during proestrus in the rat, acute administration of NPY is inhibitory in castrated animals and we have shown that chronic administration of NPY inhibits both the gonadotropic and somatotropic axis in adult female rats. In order to further analyse the role of NPY during sexual maturation, a model of delayed sexual maturation imposed by food restriction and return to ad-libitum feeding was used. Young female rats were restricted to 7-8 g food daily starting at 24 days of life (d). This restriction completely prevented sexual maturation. At 50 d, ICV cannulas were placed and at 60 d, Alzet minipumps either delivering NPY (18 micrograms/day) or vehicle into the ICV cannula were implanted dorsally. At 61 d, rats were switched to ad-libitum feeding, a change that produced vaginal opening within 4 days in all vehicle-treated rats. In the rats receiving NPY, significantly increased food intake and weight gain were observed but only one out of the 9 rats studied experienced vaginal opening at 66 d, the other 8 animals remaining sexually immature at 67 d at sacrifice. Sexual immaturity of NPY-treated rats was further confirmed by decreased ovarian weight and reduced number of pituitary GnRH receptors. Plasma IGF-I levels were markedly reduced in NPY-treated rats. Since food restriction has been shown both to increase hypothalamic NPY and to reduce or inhibit sexual function, these data bring evidence for the first time that NPY could be involved in the inhibition of sexual maturation imposed by food restriction, since maintenance of elevated NPY levels in the hypothalamus did prolong this state of sexual immaturity despite restoration of normal food intake.

Animals↗
PubMed1993

Serum bioactive gonadotropins during male puberty: a longitudinal study.

To evaluate the relative changes in serum bioactive (B) and immunoreactive (I) plasma gonadotropin concentrations during pubertal maturation, 28 healthy boys were enrolled at Tanner stage I and followed at 6-month intervals until achievement of Tanner stage V of pubertal maturation. At each visit, a careful interview, complete physical examination, sexual maturation staging, and bone age x-ray study were done, and a blood sample was obtained. Serum concentrations of PRL, dehydroepiandrosterone, and its sulfate, delta 4-androstenedione, estrone, estradiol, and testosterone (T) were determined by RIA. Samples from 20 boys were assayed for I-LH by RIA and for B-LH by the rat interstitial cell testosterone production assay, using 2 standards [Second International Reference Preparation-Human Menopausal Gonadotropin (2nd IRP-hMG) and LER 960]. Samples from 11 boys (3 from LH group and 8 others) were assayed for I-FSH by RIA and B-FSH by the rat Sertoli cell aromatase induction assay. The results were analyzed by regression analysis for B and I LH and FSH by Tanner stages of puberty, and by correlation of B to I LH and FSH as well as B and I LH and FSH to T. The results from both LH standards correlated well to each other (r = 0.967 and 0.882 for B- and I-LH, respectively), and the data are presented for 2nd IRP-hMG standard. In both groups of boys serum T concentrations increased progressively with pubertal development (P < 0.001). The boys bone age, testicular volume, serum T, dehydroepiandrosterone sulfate, dehydroepiandrosterone, delta 4-androstenedione, estrone concentrations correlated well with pubertal maturation, similar to previously published data and indicate that this group of boys had progressed through puberty in the expected normal manner. Mean serum I-LH concentrations increased progressively from Tanner stage I to V of puberty (P < 0.001), and serum B-LH exceeded the increase in serum I-LH levels. Mean serum I-LH concentrations were 2.0 +/- 0.1, 2.9 +/- 0.2, 4.7 +/- 0.4, 6.7 +/- 0.7, and 10.4 +/- 2.0 IU/L 2nd IRP-hMG whereas mean serum B-LH concentrations were 0.8 +/- 0.1, 2.2 +/- 0.2, 5.9 +/- 0.2, 10.3 +/- 1.2, and 22.3 +/- 3.8 IU/L 2nd IRP-hMG for Tanner stages I-V of puberty, respectively. This resulted in a progressive increase of LH B/I ratio with advancing pubertal maturation (P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex Hormones↗
PubMed1992

Comparison between short- and long-term insulin-like growth factor response to recombinant human growth hormone.

Eight growth-hormone-deficient children were treated with recombinant human GH (rhGH). Results of the short-term metabolic response to rhGH performed at the start of therapy during a 5-day introduction period and long-term results on growth were analyzed. We could not find any correlation between the effects on the short-term metabolic test and the growth response during long-term therapy, namely between the urea and insulin-like growth factor-I response during the short test and the increase in growth velocity. The short-term test is not a good predictor of the long-term response.

Adolescent↗
PubMed1992

Longitudinal monitoring of bone mass accumulation in healthy adolescents: evidence for a marked reduction after 16 years of age at the levels of lumbar spine and femoral neck in female subjects.

The amount of skeletal mass acquired during adolescence is one of the most important determinants for the risk of postmenopausal and involutional osteoporosis. In both sexes, a large variance in bone mineral density (BMD) and content (BMC) is observed among healthy individuals at the beginning of the third decade. To determine the crucial pubertal years during which bone mass accumulation mainly occurs, we longitudinally monitored the gain in BMD/BMC at clinically important sites, such as lumbar spine and femoral neck, with respect to osteoporotic fracture risk. The changes in BMD (grams per cm2) and BMC (grams) were determined at 1-yr intervals at the level of lumbar spine vertebrae (L2-L4), femoral neck, and midfemoral shaft, using dual energy x-ray absorptiometry (Hologic QDR 1000), in 198 healthy adolescents (98 females and 100 males), aged 9-19 yr. Mean daily energy and calcium intakes, height, weight, and body mass index of the studied cohort were within the normal range for age. In females, the increment rate in BMD/BMC was particularly pronounced over a 3-yr period, i.e. from 11-14 yr of age. This increment dramatically fell after 16 yr and/or 2 yr after menarche. The mean gains in lumbar, femoral neck, and midfemoral shaft BMD were not statistically significant between 17-20 yr. In males, the gain in BMD/BMC was particularly high over a 4-yr period, i.e. from 13-17 yr. Then the increment rate markedly declined, but remained significant between 17-20 yr for L2-L4 BMD/BMC and midfemoral shaft BMD. In contrast, no significant increase was observed for femoral neck BMD. An impressive interindividual variation was observed between the yearly height increment and the bone mass accumulation. The bone mass-height gains relationship during puberty evolved according to a loop pattern, with maximal variance at Tanner stages P3-P4. This longitudinal study delineates the crucial pubertal years during which the skeletal mass accumulates at high, but various, rates at skeletal sites where the consequences of the osteoporosis are particularly dramatic. Furthermore, the results indicate that in a cohort of healthy females with apparently adequate intakes of energy and calcium, bone mass accumulation is drastically reduced by 16 yr of age in both lumbar spine and femoral neck.

Absorptiometry, Photon↗
PubMed1991

Risks of jet injection of insulin in children.

The aim of our study was to assess whether a non-invasive insulin injector could improve the metabolic control of ten diabetic children complaining of painful injections with syringe and needle. The cumulative study period amounted to 1347 days. Whereas a non-significant rise in insulin needs was observed (from 0.98 +/- 0.03 to 1.03 +/- 0.06 units/kg per day, mean +/- sem), mean HbA1c value remained unchanged (8.9% +/- 0.4% vs 9.0% +/- 0.5%). Jet injections were felt as less painful than those using syringe and needle (nine out of ten cases). This advantage was hampered by side-effects in eight out of ten cases such as episodes of glycoketonuria (six out of ten cases) leading to hospitalization in three patients. Other side-effects included inability to adjust injection pressure (four out of ten cases) and technical failure requiring an exchange of injector in five cases. The four children with most serious problems were significantly younger (P = 0.009) than other subjects. In conclusion, this type of injector should be discouraged in young diabetic children. For older children and adolescents, it may be an alternative to syringe and needle provided repeated detailed information and tight medical supervision is available.

Adolescent↗
PubMed1990

[Immunosuppression in Type I diabetes mellitus].

The etiopathogenesis of type I or insulin-dependent diabetes mellitus is not known in details. It is now generally accepted, that type I diabetes is the result of an autoimmune disease. Type I diabetes begins after the destruction of 80-90% of insulin-producing beta cells in the pancreas. This knowledge let to immune intervention trials with various immunosuppressive drugs, especially cyclosporine A. These studies are still in an experimental stage. Because of inefficiency and severe side effects of these drugs, the med.-scientific section of the Swiss Diabetes Association recommends not to use immunosuppressive drugs in newly diagnosed patients with type I diabetes.

Autoimmune Diseases↗
PubMed1990

Serum bioactive follicle-stimulating hormone concentrations from prepuberty to adulthood: a cross-sectional study.

Serum bioactive (B) LH concentrations increase with each pubertal stage and exceed immunoreactive (I) measurements in boys and girls throughout puberty. These results have been attributed to increased GnRH secretion and/or sex steroid modulation. FSH secretion is likewise affected by these factors. We, therefore, tested the hypothesis that serum B-FSH concentrations would increase with each stage of puberty in boys and girls. In this study we compared the serum concentrations of B-FSH, I-FSH, and sex steroids and stages of puberty (determined according to Tanner) in 111 sera obtained from boys and girls from 6-18 yr of age with the results obtained from 6 young men under the age of 35 yr and 13 cycling women (studied during the follicular, periovulatory, and luteal phases of their menstrual cycles). The serum I-FSH, testosterone (T), and estradiol (E2) concentrations were determined by RIAs, and B-FSH was determined by the rat Sertoli cell aromatase induction assay. The results were analyzed by one-way analysis of variance followed by Scheffe's test for each gender and two-way analysis of variance followed by Student-Newman-Keuls test for comparison of the results between sexes. In boys the mean serum T concentrations increased progressively with each stage of pubertal development up to Tanner stage 4 (P less than 0.01). The mean serum I-FSH concentration at Tanner stage 1 was 0.7 +/- 0.1 ng/mL (hFSH-3) and did not change significantly until Tanner stage 4, when it was increased to 3.7 +/- 1.0 ng/mL (P less than 0.05). The mean serum I-FSH concentrations for Tanner stage 5 and adult men were not statistically different, but were lower than in Tanner stage 4. Mean serum B-FSH concentrations measured with the same standard were 1.9 +/- 0.4, 3.1 +/- 0.4, 2.7 +/- 0.4, 4.2 +/- 1.4, and 3.6 +/- 0.3 ng/mL in Tanner stages 1-5, respectively. These were not significantly different. In girls the mean serum E2 concentrations increased progressively between the Tanner stages (P less than 0.00005, by two-way analysis of variance). Mean serum I-FSH levels did not change significantly with the achievement of different pubertal stages. The mean B-FSH concentrations were 2.7 +/- 0.4, 2.8 +/- 0.5, 3.8 +/- 0.8, 2.8 +/- 0.7, and 3.9 +/- 0.6 ng/mL at Tanner stages 1-5, respectively, and were, likewise, not statistically significantly different. In adult women the mean serum B-FSH concentrations during the follicular phase of the menstrual cycle were not significantly different from pubertal values.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

Urinary excretion of [D-Ser(t-Bu)6,Des-Gly10]GnRH ethylamide (buserelin) during therapy of central precocious puberty: a multicentre study.

In order to compare the clinical effects of buserelin on central precocious puberty to its excretion in urine, as a parameter of metabolism or compliance, we have studied 52 patients treated either sc or intranasally. In girls with good control, urinary buserelin excretion represented 0.5 +/- 0.1% of the daily intranasal dose vs 12.5 +/- 2.3% of the daily sc dose. In boys, it represented 0.8 +/- 0.2 and 9.9 +/- 2.7%, respectively. In the sc treated group, 3 patients (2 girls and 1 boy) with poor control who exhibited excretion levels similar to those with good control were classified as resistant to therapy. Clinical control was poor in 4 intranasally treated girls: 2 had low excretion values suggesting poor compliance or failure of absorption by the nasal mucosa, and 2 appeared resistant to therapy, as urinary excretion levels of buserelin were similar to those of well-controlled patients. In addition, these data suggest that the small amount of buserelin absorbed by the nasal mucosa, as expressed by urinary excretion, is sufficient to desensitize the pituitary gonadotropes without any significant first-pass effect in the systemic circulation. This may explain the clinical effectiveness of the intranasal route for administration of small hormonal peptides acting on the pituitary gland.

Administration, Intranasal↗
PubMed1989

Growth and pubertal development of young female gymnasts and swimmers: a correlation with parental data.

Whereas intensive and regular physical training is known to alter female reproductive function, its potential role in growth is still controversial. At the beginning of a longitudinal growth study of young elite female gymnasts (n = 34, 15-25 h/wk training) and moderately trained swimmers (n = 19, 5-15 h/wk), patterns of recalled parental growth and pubertal maturation were compared with those of parents of 25 sedentary school girls. These data were also correlated to the height, weight, pubertal development as well as adult height prognosis of their daughters. Bone age was estimated using the methods of Greulich-Pyle and Tanner (RUS score) and adult height prognosis using the methods of Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT), and Tanner et al. (TW2). Parents of gymnasts were significantly lighter (fathers: P = 0.027; mothers: P = 0.038) and shorter (fathers: P = 0.034; mothers: P less than 0.001) than those of swimmers and controls. Consequently, target heights of gymnasts were also significantly shorter (P less than 0.001). Recalled menarche occurred significantly later (P = 0.030) in mothers of gymnasts who, in turn, grow much alike their mothers. At the first visit, the gymnasts were shorter and lighter for age than swimmers and controls. Their bone age (11.0 +/- 1.3 years, mean +/- SD) was retarded (P less than 0.001) when compared with chronological age (12.6 +/- 1.2 years). Adult height prognosis was lower for gymnasts than for other girls (BP: P less than 0.001; RWT: P = 0.023, TW2: P less than 0.001), but adequate for target height range.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Determination by Skeleton↗
PubMed1989

Modulation of the neonatal pituitary and adrenocortical responses to stress by thyroid hormones in the rat: effects of hypothyroidism and hyperthyroidism.

Neonatal rats exhibit a period of diminished pituitary and adrenocortical responses to stress during the first 2 weeks of life. Since thyroid hormones are known to affect brain development, modulation of these responses to stress by alterations in thyroid hormone status have been investigated in hypothyroid (Hypo) and hyperthyroid (Hyper) rat pups. Changes in ACTH and corticosterone (B) levels were measured under basal and stress conditions (3 min exposure to ether vapors) in neonates of various ages (day 5-21). Basal T4 and corticosterone-binding globulin (CBG) levels were also measured. Hypo pups were obtained from methimazole-treated mothers and hyperthyroidism was induced by daily subcutaneous injections of L-T4 (100 micrograms/kg BW) from birth on. In Hyper rats, premature onset of ACTH and B responses to stress was observed in 5-day-old rats while significant ACTH and B secretion only appeared by day 10 in vehicle-injected rats. By contrast, ACTH and B responses to stress were delayed in Hypo pups and only occurred by day 21. The lack of ACTH and B responses to stress of 14-day-old Hypo rats could be reversed by one single L-T4 injection (100 micrograms/kg BW) given 24 h, but not 4 h prior to exposure to stress. On day 21, smaller (p less than 0.05) stress-induced ACTH release was observed both in Hypo and Hyper rats compared to intact rats, concomitant with a diminished ACTH secretion following exogenous ovine CRF (10 micrograms/kg BW, i.p.) administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1989

Developmental pattern of 17 beta-hydroxysteroid dehydrogenase and 5 alpha-reductase activities in the foreskin of boys from birth to eight years of age.

The normal developmental pattern of 17 beta-hydroxysteroid dehydrogenase (17HSD) activity in genital skin was examined using radiolabeled androstenedione as a substrate in a microassay based on high-pressure liquid chromatography separation of the metabolites. This assay allowed the simultaneous determination of 17HSD and 5 alpha-reductase (5R) activities in both individual foreskin samples and pools of tissue obtained at circumcision from birth to 8 years of age. The results show that 17HSD activity is very low at birth and increases steadily during the so-called quiescent period. Reciprocal changes were observed for 5R. The increase in 17HSD activity appears to be independent of gonadal stimulation, but the mechanisms involved remain to be elucidated. From a clinical standpoint, our results provide an alternative explanation for the relative lack of virilization observed in newborns with testicular 17HSD deficiency.

17-Hydroxysteroid Dehydrogenases↗
PubMed1989

Growth hormone (GH) deprivation induced by passive immunization against rat GH-releasing factor delays sexual maturation in the male rat.

GH deprivation after passive immunization against rat GRF (rGRF) markedly affects somatic growth in male rats. Since it has been postulated that GH and probably insulin-like growth factor-I (IGF-I) might have a permissive role on sexual maturation, the effects of GH deprivation on the course of sexual maturation were tested. Male rats were treated with a potent anti-rGRF serum between 15 and 39 days of life (0.25 ml administered sc every second day). Body weight of treated rats averaged 62% of that of control (normal rabbit serum-treated) rats at 40 days of life (d), and 64% at 50 d after which age, treated rats started to grow normally. At 40 and 50 d, pituitary GH content was very much depressed (representing approximately 20% of control values at both ages), plasma GH was undetectable, and plasma IGF-I levels averaged 30% of those of control rats. At 70 d, 30 days after cessation of treatment, pituitary GH content, and IGF-I secretion were almost normal. At 40 d, testes and seminal vesicles of treated rats were small-for-age in agreement with significantly decreased plasma levels of FSH and delayed spermatogenesis characterized by the presence of only few or no spermatozoa. At 50 d, 10 days after cessation of anti-rGRF injections, progress of sexual maturation was found to be consistent with age and coincided with normalization of growth rate. At 40 and 50 d, pituitary contents of FSH and LH were severely decreased but became normal at 70 d. In conclusion, GH deprivation which markedly affected somatic growth induced a transient delay of sexual maturation. GH deficiency seems to have affected mostly the synthesis and secretion of FSH, thus producing a delay in testes growth and in the differentiation of the germinal cells. The low levels of IGF-I might also have been the cause for the delay of maturation at the pituitary and/or the gonadal levels.

Animals↗
PubMed1989

Differences between circadian and ultradian organization of cortisol and melatonin rhythms during activity and rest.

We compared the cortisol and melatonin circadian and ultradian rhythms in normal men using two approaches: 1) the men were exposed successively to two conditions, one normal and a second chosen to alter differently each of the hormones, i.e. complete bedrest for 34 h (supine, fasting, and under dim light), and 2) analyses of the rhythms using a combination of curve smoothing for the description of the 24-h rhythm, and peak detection and spectral analysis for the measurement of periodic phenomena. Blood was sampled every 30 min from 0700-0700 h. A diurnal rhythm was detected for both hormones, with different underlying frequencies. Plasma cortisol had an ultradian rhythm of 8 h. From 0000-0800 h (night) and 0830-1600 h (early day), the pulsatile activity and baseline values of cortisol were high, while from 1630-2400 h (late day), these variables were low. During complete bedrest, pulsatile activity and baseline values were even higher during the night period, and the nocturnal peak of cortisol, usually present between 0300-1000 h, was split in two, with an early peak at 0000-0400 h. There were two specific events during the day associated with synchronous, high amplitude pulses: awakening and eating at noon. No such pulses occurred at suppertime or when the men fasted. Melatonin secretion was organized around a 5.5-h period. In the rest condition, plasma melatonin values were higher during the night. The 24-h rhythms of cortisol and melatonin were temporally related. Plasma melatonin began to rise when plasma cortisol was at its lowest, it peaked when cortisol began to rise, and it began to decrease when cortisol reached its peak, with a 5-h phase delay between plasma cortisol and melatonin rise at night. In summary, melatonin and cortisol rhythms have different ultradian frequencies, suggesting an intrinsic difference in the mechanisms controlling their secretion. In addition, their responses to restricted physical activity in an environment with dim light were completely different; for plasma melatonin, the change was primarily quantitative, with an increase in total production especially at night, while for plasma cortisol, there was more of a qualitative change, with different patterns of pulsatile activity and possible splitting of the nocturnal peak. The differences in the ultradian organization of these two hormones imply that the correlation between their peaks must depend on a third factor, which is likely to be the 24-h organization of the day.

Activity Cycles↗
PubMed1989

Physiology of puberty.

Adolescence represents the period of important somatic changes which lead to sexual maturation, pubertal growth and active functions of reproduction. Mean ages of onset of puberty are 10.9 and 11.2 in girls and boys respectively. Menarche occurs at a mean age of 13.4 yr and may be related to a critical weight. In boys, testicular growth above 4 cm2 or 4 ml is the first clinical sign of gonadal pubertal maturation. In girls, the first sign is the budding of the breast. At onset of puberty, the hypothalamus after a "quiescent" period resumes a marked pulsatile secretion of gonadotrophin-releasing hormone, leading to an increased secretion of pituitary gonadotropins which in turn stimulate the gonadal functions, i.e. the secretion of testosterone or estradiol and maturation of the spermatogenesis or the ovarian follicle. Neuroendocrine factors which probably control the onset of puberty are numerous: cerebral adrenergic and/or dopamine neurotransmitters, endogenous opioids, melatonin from the pineal gland. Gonadal maturation (gonadarche) is preceded in the infant by a post-natal surge of luteinizing hormone and at age 7 to 8 yr by an adrenal maturation (adrenarche).

Adolescent↗
PubMed1989

Growth in a case of Russell-Silver syndrome treated for hypopituitarism.

The growth characteristics of Russell-Silver syndrome (RSS) include dwarfism of prenatal onset, moderate retardation of bone age and normal postnatal height velocity. We describe a case of hypopituitarism in a girl with typical RSS who suffered from a severe trauma at birth. Signs of hypopituitarism appeared during childhood. Before substitutive treatment, a short course of human growth hormone (hGH) induced a moderate rise in plasma IGF-I levels which was within the range observed in other pituitary dwarfs. Under replacement therapy, catch-up growth was similar to what is observed in other growth hormone deficient children. However, bone age matured much faster than chronological age. This observation appears to be a particular feature of RSS, possibly enhanced by hGH therapy. An improvement of adult height beyond the final height usually observed in RSS children without endocrine disturbances should therefore not be expected from hGH therapy. Growth hormone deficiency and RSS do not appear to be causally related. However, in each child with RSS, a particular attention should be given to a decreased height velocity, a severely delayed bone age as well as a history of major perinatal problems. Should one of these factors be found, a careful evaluation of the hypothalamo-pituitary axis ought to be performed with, accordingly, an appropriate substitutive therapy.

Child↗
PubMed1988

Delayed sexual maturation induced by daily melatonin administration eliminates the LH response to naloxone despite normal responsiveness to GnRH in juvenile male rats.

Daily administration of melatonin (MT) markedly delays sexual maturation in the male Wistar rat. In this study, we have evaluated pituitary responsiveness to GnRH and the level of tonic inhibition by endogenous opioids in normal juvenile male rats and in rats with delayed sexual development induced by daily afternoon MT injection (100 micrograms, s.c.) starting at 20 days of life. Plasma LH responses to repetitive intravenous GnRH administration (100 ng/100 g body weight), or to different doses of GnRH administered subcutaneously (5-100 ng/100 g body weight) were normal in MT-treated rats both at 30 and 40 days of life despite significantly lower number of pituitary GnRH receptors and decreased pituitary gonadotropin content. One naloxone (NAL) injection (2.5-5.0 mg/kg, s.c.) produced a significant increase of plasma LH in normal 40- and 55-day-old rats, which was not seen in MT-treated rats of the same age. In contrast, no increase of plasma LH was seen in 30-day-old control rats nor in MT-treated rats at this age. Pretreatment with morphine sulfate (10 mg/kg, s.c.), or with the potent Met-enkephalin analog FK 33-824 (1.0 mg/kg, s.c.) prevented the NAL-induced rise of plasma LH in control rats at day 40 of life. In all instances, plasma PRL levels were decreased after NAL both in untreated and in MT-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗