Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Puberty, Delayed”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37Linked to original sources
PubMed1992

Effects of rat alpha-fetoprotein administration on estradiol free fraction, the onset of puberty, and neural and uterine nuclear estrogen receptors.

The cause of the onset of puberty in the rat or any other mammalian species is unknown. According to one theory, puberty is initiated through switching of the brain "gonadostat." It is hypothesized here that puberty in the rat is the consequence of the appearance of free, and therefore physiologically active, estrogen in the circulation. To test this, the unbound fraction of estradiol in serum of immature female rats was measured in relation to the nuclear receptor occupancy of estradiol in the hypothalamus, preoptic area, and uterus at various times after birth. In addition, an attempt was made to alter the free fraction of estradiol by injection of the estradiol-binding protein alpha-fetoprotein (AFP) into immature female rats. The free fraction of estradiol was low (less than 1%), but began rising at about 20 days of age, and a significant increase in nuclear bound estradiol was observed in 23-day-old rats (P less than 0.001). By day 30, unbound levels attained adult values (3.99 +/- 0.15%). At this time, nuclear bound estradiol in all tissues examined fell (P less than 0.01), but by day 40, these were greatly increased in rats in estrus (P less than 0.001), being trebled in the preoptic areas and doubled in the hypothalamus. Injection of AFP into immature female rats extended the period of low free estradiol (1.22 +/- 0.08%), while in albumin-injected rats, the free fraction was 4.44 +/- 0.1%. Injection of AFP resulted in levels of nuclear-bound estradiol that were less than half those measured in nuclei from AFP-injected animals (P less than 0.001), and AFP delayed puberty. The affinity of the reaction between estradiol and nuclear receptors in brains of immature and mature rats was not significantly different; the Kd fell within the range of 0.05-0.08 nM. It is suggested that in the rat, puberty is the result of the appearance in the circulation of physiologically active estradiol after day 20.

Animals↗
PubMed2003

Effects of flaxseed and defatted flaxseed meal on reproduction and development in rats.

Flaxseed, a rich source of reportedly beneficial n-3 fatty acid and phytoestrogens, has not been thoroughly tested for reproductive effects. High levels of flaxseed (FS, 20 or 40%) or defatted flaxseed meal (FLM, 13 or 26%) added to AIN-93 diet were evaluated in a two-phase study: dosed during gestation only or during gestation and maturation in a lifetime study. At cesarean section on gestation day 20, neither FS nor FLM affected fertility, body weight gain, litter size, or fetal development. FLM, but not FS, decreased gestation length. The offspring of dams allowed to litter were observed to postnatal day (PND) 21 or 90. Neither FS nor FLM affected PND 21 survival indices of F1 pups. FS (20 and 40%), but not FLM, increased the anogenital index (AGI) of F1 females at PND 21. The AGI of F1 males was not affected by either FS or FLM. FLM (13 and 26%), but not FS, delayed puberty in F1 males. Age and weight at the onset of puberty in females were not affected by FS or FLM. FS and FLM caused dose-related increases in the number of F1 females with irregular estrous cycles. During PND 21-90, F1 females fed 20% FS, 13% FLM, or 26% FLM gained more weight than the controls. FS and FLM decreased thymus/body weight and thymus/brain weight ratios in weanling F1 males and females. FS and FLM decreased liver/body weight and liver/brain weight ratios in weanling F1 females, and 26% FLM decreased the same two ratios in F1 males. In conclusion, FS did not affect fetal development but did affect indices of postnatal development such as the estrous cycle.

Abnormalities, Drug-Induced↗
PubMed2000

Maternal exposure to tamoxifen during pregnancy increases carcinogen-induced mammary tumorigenesis among female rat offspring.

Tamoxifen is under investigation as a potential chemopreventive agent in women of child-bearing age who are at an increased risk to develop breast cancer. However, because tamoxifen may act as an estrogen in the fetus and high fetal estrogenic activity, in turn, may increase subsequent breast cancer risk, we wanted to determine the effects of a maternal exposure to tamoxifen during pregnancy on offspring's susceptibility to mammary tumorigenesis. Pregnant rats were injected s.c. with 20 microg of tamoxifen or oil vehicle daily during days 15 and 20 of gestation. In utero exposure to tamoxifen caused abnormalities in the development and function of the reproductive track, including a delayed puberty onset and changes in uterine wet weights. The tamoxifen-exposed offspring, treated with 7,12-dimethylbenz[a]antracene (DMBA) at the age of 45 days, developed an increased incidence of mammary tumors. In week 18 after DMBA administration, 50% of the vehicle-controls had developed mammary tumors, whereas tumor incidence in the tamoxifen group was 95%. In addition, a significantly higher number of tumors in the tamoxifen-exposed group kept growing (rather than stopped growing or regressed) than in the control group. Furthermore, histopathological examination revealed that the mammary tumors in the tamoxifen offspring were less differentiated and exhibited a more aggressive phenotype, compared with the tumors growing in the controls. These results suggest that a maternal exposure to tamoxifen during pregnancy acts as an estrogen in the fetal mammary gland and increases the susceptibility to breast cancer among female offspring.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2006

Disruption of testosterone homeostasis as a mode of action for the reproductive toxicity of triazole fungicides in the male rat.

Triazole fungicides associated with a range of reported male reproductive effects in experimental animals were selected to assess potential toxic modes of action. Wistar Han rats were fed myclobutanil (M: 100, 500, or 2000 ppm), propiconazole (P: 100, 500, or 2500 ppm), or triadimefon (T: 100, 500, or 1800 ppm) from gestation day 6 to postnatal day (PND) 120. One male per litter was necropsied on PND1, 22, 50, or 92. Measurements included anogenital distance (AGD) at PND0, body and organ weights, serum hormone levels, age at preputial separation (PPS), sperm morphology and motility, and fertility and fecundity. AGD was increased by the high dose of all three triazoles, indicating hypervirilization. Triadimefon delayed PPS, consistent with delayed puberty, at 1800 ppm. Relative liver weights were increased at PND1, 50, and 92 by all three triazoles. Hepatocellular hypertrophy was present at PND50 from propiconazole and triadimefon and at PND92 from all three high-dose triazole treatments. Relative pituitary weights were decreased at PND92 by middle- and high-dose myclobutanil treatment. Absolute testis weights were increased at PND1 by myclobutanil, at PND22 by myclobutanil and triadimefon, and at PND50 by propiconazole and triadimefon treatment. Relative ventral prostate weights were increased at PND92 by myclobutanil and triadimefon treatment. Serum testosterone was increased at PND50 by triadimefon and at PND92/99 by all three triazole treatments. Insemination and fertility were impaired by myclobutanil and triadimefon treatment. In addition to the reproductive system effects, total serum thyroxine levels were decreased at PND92 by high-dose triadimefon. These reproductive effects are consistent with the disruption of testosterone homeostasis as a key event in the mode of action for triazole-induced reproductive toxicity.

Anal Canal↗
PubMed1990

Metabolic interfaces between growth and reproduction. III. Central mechanisms controlling pulsatile luteinizing hormone secretion in the nutritionally growth-limited female lamb.

Growth retardation induced by dietary restriction in the lamb results in a low frequency of episodic LH secretion and, thus, delayed puberty. Such lambs respond normally to physiological doses of GnRH, indicating that the pituitary gland can function adequately during diet-induced hypogonadotropism. The current studies investigated central mechanisms underlying diet-induced hypogonadotropism. The first aim was to determine whether the hypothalamic GnRH secretory system is capable of normal function. The initial approach was to compare hypothalamic GnRH content between lambs on a restricted diet with low LH pulse frequency (less than 1 pulse/4 h; n = 5) and lambs on an ad libitum diet with high LH pulse frequency (4.5 +/- 0.4 pulses/4 h; n = 5). RIA of extracts of preoptic area and mediobasal hypothalamus/median eminence tissue blocks revealed no differences in GnRH content between lambs on a restricted diet and those on an ad libitum diet. The second approach was to determine if LH secretion could be induced by chemical stimulation of neuronal function with N-methyl-D,L-aspartate (NMA), an excitatory amino acid agonist. Initially, a single iv bolus of NMA was given to hypogonadotropic lambs on a restricted diet. There was a dose-dependent immediate rise in serum LH concentrations. All lambs responded to the highest dose (5.0 mg/kg BW; n = 6), and four of five lambs responded to the intermediate dose (1.0 mg/kg). No lambs responded to the lowest dose (0.2 ng/kg), despite a normal response to GnRH (2.5 ng/kg BW, iv). In a second experiment, hypogonadotropic lambs on a restricted diet were treated with repeated injections of NMA (5 mg/kg BW, iv) at either hourly intervals (n = 6) or every 3 h (n = 6). Each NMA injection induced a LH pulse in both treatment regimens over the entire 7-h experimental period. Thus, the nutritionally growth-limited lamb is capable of sustained production of LH pulses, which, we presume, reflect GnRH secretion. The second aim was to test the hypothesis that endogenous opioid mechanisms inhibit LH secretion during nutritionally induced hypogonadotropism, because opioid pathways are a poor inhibitory regulator of LH secretion in the normally developing sheep, even in the absence of ovarian steroids. We were unable to detect any effects of the opiate antagonist naloxone on LH secretion in the nutritionally growth-limited lamb. We conclude that central mechanisms controlling the release, rather than synthesis, of GnRH are limiting LH secretion when sexual maturation is delayed by growth retardation. Moreover, opioid inhibition is not the primary reason for hypogonadotropism during dietary restriction.

Animals↗
PubMed1981

Cavernous hemangioma in the diencephalon.

A 32-year-old man with a history of delayed puberty and obesity was seen initially with bitemporal hemianopsia and headache in 1974. Neuroradiologic studies showed a mass in the chiasmatic cistern and hypothalamus. Surgical exploration of the chiasm was unrevealing. Slowly progressive memory loss and intellectual impairment developed. Necropsy in 1978 disclosed a large cavernous hemangioma in the diencephalon.

Adult↗
PubMed1984

Short stature and pubertal delay in male adolescents with cystic fibrosis. Androgen treatment.

We evaluated the growth rate and pubertal status of 54 adolescent and young adult men with cystic fibrosis and assessed the efficacy of short-term androgen therapy in promoting growth and pubertal development. Thirty-nine percent were below the fifth percentile in height and 8/28 (28%) between the ages of 14 and 18 had delays in pubertal development. Five male adolescents aged 13 years 8 months to 18 years 3 months were treated with testosterone and their conditions were prospectively evaluated. Growth rate increased from an entry mean of 2.2 cm/yr (range 0 to 4 cm/yr) to 7.2 cm/yr (3 to 10 cm/yr). We conclude that a brief course of testosterone appears to be a safe, effective means of improving growth rate in male adolescents with cystic fibrosis with delay of puberty.

Adolescent↗
PubMed1991

Angiofollicular lymph node hyperplasia (Castleman's disease) in an adolescent female. Clinical and immunologic findings.

Angiofollicular lymph node hyperplasia is a heterogeneous disorder of unclear etiology and has a wide spectrum of systemic symptoms. This report describes a case of this disorder in a 15-year-old girl and examines the response of the primary mass, systemic symptoms, and alterations of selected immune parameters at diagnosis, as a result of steroid therapy and radiation therapy (RT). The patient had a 1-year history of growth failure, delayed puberty, and refractory iron deficiency anemia. Computed tomography scan showed a posterior mediastinal mass. Biopsy revealed angiofollicular lymph node hyperplasia of mixed hyaline-vascular and plasma cell type histologic type. Immunoperoxidase studies showed polyclonal B-cells, predominance of T-helper cells (CD4) over cytotoxic/suppressor T-cells (CD8), and the presence of natural killer (NK) cells. Southern blot analysis demonstrated germ line gene configuration for the T-cell antigen receptor and Ig heavy chain. The patient clinically improved with RT after failing to respond to steroids. Immunophenotyping of peripheral blood lymphocytes before therapy revealed a CD4:CD8 ratio of 0.8 with decreased numbers of circulating T-cells; this increased to 1.4 after steroid therapy. The patient's T-lymphocytes had no proliferative response to phytohemagglutinin (PHA) or concanavalin A (Con A) before RT. After RT, a small but significant mitogenic response to these reagents was noticed. The proliferative response to recombinant interleukin-2 (rIL-2) remained similar to that of control lymphocytes. Induction of second messenger signals by activation of protein kinase C (PKC) and elevation of free cytosolic calcium through the use of the phorbol ester, phorbol 12, 13-dibutyrate (PDBu), and ionomycin (Io) resulted in a strong proliferative response at diagnosis and after RT. In vitro cytotoxicity assays revealed diminished NK activity before and after therapy. Lymphokine-activated killer (LAK) activity remained comparable with that of control cells and was not affected by therapy. Before RT patient lymphocytes maintained cytotoxic capabilities after coincubation with rIL-2 and PDBu plus Io, whereas coincubation with these reagents abrogated cytotoxic function of normal cells. This case demonstrates a clinical response to RT as well as improvement in immune parameters. Intact signal transduction mechanisms through PKC activation and elevation of cytosolic calcium were also demonstrated in the circulating lymphocytes.

Adolescent↗
PubMed1983

An X;9 translocation, primary amenorrhea, and hypothalamic dysfunction.

A white girl presented at age 16 yr with delayed puberty and primary amenorrhea. She had 46 chromosomes with a de novo reciprocal X;9 translocation. The normal X chromosome was found to be heterochromatic, thus preserving the function of the translocation portion of the 9. Her total estrogen and serum estradiol levels were low and her serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were at the lower end of the normal adult range. She had a reasonably good FSH and LH response to GnRH, but an inadequate response to 100 mg of clomiphene daily for 1 wk. This would suggest that the abnormality of function is probably hypothalamic, a hitherto unreported association. De novo translocations between X chromosomes and autosomes are rare and none identical to this case has been described. The breakpoint of the X chromosome was at p22, well outside the "critical region" for female reproductive function. It seems probable that her chromosome abnormality is responsible for her clinical state.

Adolescent↗
PubMed1990

Trichothiodystrophy, mental retardation, short stature, ataxia, and gonadal dysfunction in three Moroccan siblings.

Three sibs, a boy and two girls, born to Moroccan consanguineous parents, were affected with a syndrome characterized by brittle hair, mental retardation, short stature, ataxia, and gonadal dysfunction. The hair in these three patients displayed the morphological and biochemical hallmarks of trichothiodystrophy (TTD). Gonadal function tests showed abnormal gonadotropic responses to LHRH, consistent with delayed puberty in the male and ovarian failure in both females. Comparison with previously reported cases of TTD associated with mental retardation suggests genetic heterogeneity, although specific biochemical markers are needed in order to answer this question.

Abnormalities, Multiple↗
PubMed1999

The molecular basis of human hypogonadotropic hypogonadism.

Patients with hypogonadotropic hypogonadism (HH) present with delayed puberty, infertility, and low serum gonadotropins. The molecular basis for most cases of HH is unknown, but single gene mutations have been described for some hypothalamic and pituitary genes. Kallmann syndrome due to KAL gene mutations and adrenal hypoplasia congenita/HH caused by AHC gene mutations are both X-linked recessive disorders. Mutations in the gonadotropin releasing hormone receptor, leptin, and the leptin receptor cause autosomal recessive HH. In addition, isolated deficiencies of follicle stimulating hormone and luteinizing hormone in the corresponding specific beta-subunit genes and PROP1 gene mutations represent pituitary deficiency states, resulting in a phenotype of HH. Despite these remarkable advances in our understanding of human HH, the cause of approximately 90% remains unknown.

Genes, Recessive↗
PubMed1998

2,3,7,8-Tetrachlorodibenzo-p-dioxin in pregnant Long Evans rats: disposition to maternal and embryo/fetal tissues.

Prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interferes with fetal development at doses lower than those causing overt toxicity in adult animals. In a multigeneration study (Murray et al., 1979), female rats that were administered 0.01 microgram TCDD/kg/day in their diet did not experience reduced fertility; however, reduced fertility was seen in the F1 and F2 generations. Exposure to TCDD during development produces alterations in the reproductive system of the developing pups, such as delayed puberty and reduced sperm counts in males (Mably et al., 1992a; Gray et al., 1995) and malformations in the external genitalia of females (Gray and Ostby, 1995). Therefore, the objectives of this study were to determine maternal and fetal tissue concentrations of TCDD that are associated with the adverse reproductive effects seen by Gray and co-workers. Pregnant Long Evans rats received a single oral dose of 1.15 micrograms [3H]TCDD/kg on Gestation Day (GD) 8 and maternal as well as fetal tissue concentrations of TCDD were measured on GD9, GD16, and GD21. On GD9, the highest level of TCDD localized in the maternal liver (25.1% dose). In addition, the amount reaching all the embryos on GD9 was 0.01% of the administered dose, which resulted in a concentration of 0.02% dose/g. The amount of TCDD reaching the fetal compartment (fetuses + placentas) increased to 0.12% dose/tissue on GD16 and 0.71% by GD21. The concentration of TCDD within the fetal compartment (0.01% dose/g) on GD16 was comparable to that found in the maternal blood and spleen. Concentrations of TCDD in a single embryo/fetus were 39.6, 18.1, and 22.1 pg/g on GD9, GD16, and GD21, respectively. Estimates of hepatic half-life of elimination in pregnant rats suggested that TCDD may be eliminated faster in pregnant LE rats. Therefore, measurements of biliary elimination were made in pregnant and nonpregnant LE rats to compare rates of metabolism; however, biliary elimination of TCDD is not affected by pregnancy. In conclusion, this dose administered during a critical period of organogenesis causes adverse effects on the developing reproductive system of rodents. This dose produced a body burden of 22.1 pg TCDD/g within a single fetus on GD21. This indicates that low-level TCDD exposure during the perinatal stage of life can produce adverse effects within the developing pups.

Adipose Tissue↗
PubMed1985

Rigid spine syndrome associated with tent-like configuration of the thoracic cage, cerebral lesion and delayed sexual maturation in three patients.

Three male patients with rigid spine syndrome and predominantly proximal myopathy which developed slowly from childhood are described; two cases were sporadic, one possibly hereditary. All three had the same associated signs and symptoms, differing only in degree. They had tent-like thoracic cages with very steeply sloping ribs, reduced anteroposterior diameter and reduced vital capacity. The EGGs were slightly abnormal. All the patients had some cerebral abnormality, in one case of diffuse demyelinating type. All had the signs and symptoms of slightly delayed puberty.

Adult↗
PubMed1995

Long-term outcome in aqueductal stenosis.

In this study, 78 patients with aqueductal stenosis were submitted to detailed neurodevelopmental assessment with a follow-up of 5-25 years. Sixty-eight percent of patients were categorized as normal; they either attended normal school courses or had regular jobs. Among these, 34% had some motor abnormalities (ataxia, mild hemiparesis, visual disturbances). Twenty-four percent (19 cases) were moderately disabled (trainable retardation) and 8% (6 cases) were severely handicapped. Epilepsy was observed in 13% of the cases. Incidence of recurrent and generalized seizures paralleled neurodevelopmental outcome (5% in normal, 16% in moderately disabled and 50% in severely disabled patients). Endocrine dysfunctions were evident in 28% of the cases and were characterized by precocious or delayed puberty, amenorrhea and somatic underdevelopment. No patient with ventricular enlargement and a cortical mantle width below 20 mm showed a good outcome. Large ventricles were compatible with normal mental development when compensated with a corresponding cranial vault enlargement. In patients with normal mental status and motor abnormalities, long-term CT scan findings revealed the presence of focal brain abnormalities (poroencephaly, brain atrophy, calcifications, extracerebral collections).

Adolescent↗
PubMed1986

Niemann-Pick disease type B: clinical signs and follow-up of a new case.

A girl affected by Niemann-Pick disease type B is reported. The patient presented unusual skin lesions of nummular eczematous dermatitis, signs of delayed puberty and stunted physical development, together with the typical symptoms involving visceral organs and lungs. This disease may therefore indirectly affect more body organs than assumed.

Bone Marrow↗
PubMed1992

Long-term low-dose cyclosporin A in steroid dependent nephrotic syndrome of childhood.

Therapy of steroid-dependent idiopathic nephrotic syndrome is often unsatisfactory. Since 1986 we have treated nine children (six male and three female), aged 3-16 years, with cyclosporin A (CsA) during 2.0-5.2 (median 3.1) years. All had minimal change disease on renal biopsy and had previously received cyclophosphamide. Mean daily dosage of CsA was 4.1 mg/kg (range 2.7-5.8) and mean whole blood trough level was 220 ng/ml (range 141-271). The relapse rate decreased from 3.4/patient year before CsA to 0.55 on CsA. Discontinuation of CsA or reduction below 2 mg/kg daily was always followed by a relapse. The overall relapse rate, including the period with very low-dose CsA, was 0.95/patient year. Four patients required additional low-dose alternate-day prednisone. Repeat renal biopsy showed minimal change disease in eight patients and focal segmental glomerulosclerosis in one; CsA-toxicity was mild in two and moderate in one. The latter was the only patient with slightly reduced glomerular filtration rate. Two boys with delayed puberty spontaneously matured and reached expected final height. We conclude that long-term low-dose CsA is very effective and steroid-sparing. Its use is justified in selected patients, particularly in those with numerous relapses and in male patients before and during puberty, as long as renal function and CsA-toxicity are carefully monitored.

Adolescent↗