Delay In Sexual Maturation Research Articles

Isolated Growth Hormone Deficiency: Testing the little Mouse Hypothesis in Man and Exclusion of Mutations within the Extracellular Domain of the Growth Hormone-Releasing Hormone Receptor

The phenotypic characteristics of isolated growth hormone deficiency (IGHD) type IB in humans, such as autosomal recessive inheritance, time of onset of growth retardation, diminished secretion of growth hormone (GH) and IGF-I, proportional reduction in weight and size, and delay in sexual maturation, has much in common with the phenotype of the homozygous little/little (lit/lit) mouse. Sequencing of the GH releasing hormone (GHRH) receptor in lit/lit mice has shown a single nucleotide substitution within the extracellular peptide binding domain at codon 60 that changed aspartic acid to glycine. Therefore, the GHRH receptor is a reasonable candidate gene for causing IGHD in humans. DNA from 65 unrelated healthy Caucasians of normal stature and 65 children with IGHD type IB of whom 12 did not respond to exogenous treatment with GHRH were studied. Restriction endonuclease analysis, linkage studies, and polymerase chain reaction amplification and sequencing of the whole extracellular domain including the first three membrane spanning domains of the GHRH receptor gene were performed. None of the analyses revealed any structural abnormalities in these patients with IGHD. This suggests that a lit/lit mouse equivalent is an unlikely explanation for the majority of children with IGHD. Although gross structural abnormalities in the whole gene have been ruled out in this study, mutations in the carboxyl terminus are still possible, and, therefore, the remaining part of the gene needs to be sequenced.

Workshop on perinatal exposure to dioxin-like compounds. II. Reproductive effects.

This summary report focuses on current studies on reproductive effects reported at the workshop on Perinatal Exposure to Dioxin-like Compounds and supporting data noted in the discussion. Recent laboratory studies have suggested that altered development (e.g., low birth weight, spontaneous abortion, congenital malformation) and reproductive health (e.g., fertility, sex organ development, reproductive behavior) may be among the most sensitive end points when examining the effects of dioxinlike compounds. Thus, future research should target the reproductive health of both males and females exposed postnatally and prenatally. Studies in humans are needed and are on-going. In animal models, postnatal exposure to dioxin or dioxinlike compounds has been associated with abnormal spermatogenesis and abnormal testicular morphology and size in males and with reduced fertility and endometriosis in females. In utero exposure may also produce profound reproductive consequences in both males and females including delays in sexual maturation, abnormalities in development of sexual organs, and abnormal sexual behavior. The mechanism by which dioxin-like compounds cause reproductive effects is not well delineated.

Chronic administration of neuropeptide Y into the lateral ventricle starting at 30 days of life delays sexual maturation in the female rat.

The role of neuropeptide Y (NPY) in the regulation of sexual function is still controversial. Whereas central NPY administration is stimulatory during proestrus in the rat and other species, such administration is inhibitory in castrated animals and we have shown that chronic, central infusion of NPY inhibits both the gonadotropic and somatotropic axis in adult rats. Previous studies have suggested that NPY could be involved in the triggering of the first ovulatory LH surge and a recent report indicated that a single central NPY injection given at 30 days of life could advance sexual maturation. We therefore evaluated the effect of chronic NPY administration on the timing of sexual maturation in the female rat and compared the effects obtained with those induced by a single NPY injection. Constant infusion of NPY (18 micrograms/day) into the lateral ventricle delayed sexual maturation as seen by the absence of vaginal opening, delayed ovarian growth and reduced number of pituitary GnRH receptors. This inhibitory effect was seen as long as NPY was infused. In contrast, a single NPY injection either at 30 days of life or earlier, or repeated single injections between 28 and 31 days of life, did not modify the pace of sexual maturation. Unlike what is observed in adult animals, overall food intake was only minimally increased between 30 and 37 days of life in chronically NPY-infused rats, but this increase became more important thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemophilia Growth and Development Study

The study design, research questions, and baseline data are presented from a multicenter longitudinal epidemiologic investigation of the impact of human immunodeficiency virus (HIV) infection on three areas of functioning in children and adolescents with hemophilia: physical growth and sexual maturation, immune function, and neurological and neuropsychological functioning. Sixty-nine percent (n = 333) of a population of males between the ages of 6 and 19 years with moderate to severe hemophilia participated in a comprehensive baseline examination. Approximately 62% of the study group was HIV seropositive and 38% HIV seronegative. Adjusted for age, HIV-positive participants were three times as likely as HIV-negative participants to exhibit declines in height-for-age attainment (p = 0.05), twice as likely to have delays in sexual maturation (p = 0.414), and more than three times as likely to exhibit antibody levels that were not indicative of prior exposure or vaccination (p < 0.001). In addition, analysis of a comprehensive battery of neuropsychological tests showed that HIV-positive participants were 50% more likely to show scores approximately 1 SD below expected levels in three of nine functional areas (p = NS) compared with HIV-negative participants. Entry data for this study reveal a greater likelihood for HIV-positive children and adolescents with moderate to severe hemophilia to have abnormal growth, and to exhibit antibody levels not indicative of prior exposure to disease or vaccination, which could be attributed to HIV infection. Lowered neuropsychological test performance in both groups may be attributable to the deleterious effects of chronic illness. Data are being collected from a group of non-HIV infected non-hemophiliac siblings for comparison.

Parental influences on female puberty in the monogamous California mouse, Peromyscus californicus

Sexual maturation of juvenille Peromyscus californicus females was delayed if females were housed with both parents. This delay was attributed to contact with the mother rather than the father. Sexual maturation was not affected by contact with a strange male, but puberty was delayed by contact with a strange female. In subsequent studies, the role of maternal urinary chemosignals and physical contact in delaying puberty was examined. Exposure to maternal urine or soiled bedding had no effect on sexual maturation in juvenile females. Puberty was delayed in juvenile females that had direct physical contact with their mother compared with females not exposed to their mother. Females exposed to their mother, but prevented physical contact by a double wire-mesh barrier, showed an intermediate delay in sexual maturation which did not differ significantly from either the contact or unexposed females. Thus physical contact with the mother and not a urinary chemosignal per se is necessary to delay sexual maturation in P. californicus.

Response of Broiler Breeder Females to Feed Restriction Below Recommended Levels.: 1. Growth and Reproductive Performance

Arbor Acre broiler breeders were used to determine the effects on growth and reproductive performance of quantitative feed restriction below breeder recommended levels. Feed treatments were: 8% above standard (+8%); standard feeding program (STD); and 8 (−8%), 16 (−16%), and 24% (−24%) below standard.Proportional decreases in feed allocation resulted in corresponding decreases in body weight, frequency of double-yolked eggs, and number of days in production. Egg weight, fertility, hatchability, and female mortality to 64 wk of age were not significantly (P≥.05) affected by the reduction in feed intake. Shell quality was significantly improved with the −16 and −24% feed treatments. A delay in sexual maturity caused a significant (P≤.05) decrease in average rate of lay (%hen-day) but not in total settable eggs for treatments −16 and −24% to 64 wk of age.

Feed Restriction of Turkey Breeder Hens–A Review ,

Past research on feed restriction methods with turkey breeder hens has involved the feeding of 1) high-fiber or low-energy diets, 2) low dietary protein, 3) limited quantities of feed, 4) rations on a skip-a-day program, 5) distasteful compounds, or 6) combinations of these methods. In general, feed-restricted turkey breeder hens showed a reduction in BW and a delay in sexual maturity at time of lay with no effect on fertility, hatehability of fertile eggs, and hatchability of all eggs set Egg weight was unaffected in 13 studies, but decreases and increases were reported for two and three studies, respectively. The results on egg production and feed efficiency (number of eggs/unit of feed) were more variable. Egg production decreased, increased, or had no effect in 6, 2, and 14 of the feed restriction programs, respectively. Feed efficiency of restricted hens either was poorer (two reports), improved (three studies), or had no effect (six studies). The larger parent-stock breeder candidate of today may not respond to these feed restriction programs in the same manner as the breeder hens of the 1970s and early 1980s. Most likely, more severe feed restriction programs will have to be designed to lower the BW of these larger hens.

Reliability of Tanner stage assessments in a multi-center study.

Tanner stage indices have been frequently used in research studies to characterize the level of sexual maturation among adolescents. The Cooperative Study of Sickle Cell Disease (CSSCD) is a large multi-center study in which the assessment of Tanner stage indices has been performed to describe delays in sexual maturation and correlates of delays. Rigorous training, however, in rating Tanner stages was not provided for the clinicians in the study. Data from the CSSCD were analyzed to characterize the reliability of the assessment of sexual maturation in this study, and demonstrate the potential for increasing the reliability by more careful training. In lieu of a gold standard, a maximum likelihood algorithm was employed to examine the longitudinal consistency of Tanner stage assessments. Based on the assumption that the underlying process of sexual maturation is progressive, models were developed that allowed one to estimate jointly the incidence distribution for the attainment of Tanner stages and the error rates of assessment. Estimated false-positive rates for assessing the attainment of Tanner stages from the CSSCD ranged from 2% to 19%. Estimated false-negative rates ranged from 1% to 18%. The occurrence of these errors was found not to vary markedly with the subject's age. Error rates of this magnitude can introduce considerable bias to the estimation of the distribution of Tanner stages and result in serious losses in relative efficiency. While the validity of Tanner stage indices can be demonstrated from study data, the loss in statistical efficiency and power associated with the study error rates was severe. This underscores the utility of careful training in pubertal rating for research studies.

Menarcheal Age and Endemic Goitre

A total of 13,566 school girls from 17 districts in Sri Lanka recalled their date of menarche for a study on the prevalence of goitre. Seventy-four percent (10,036) did not have any signs of goitre, and the recalled mean age of menarche for this group was 13.6 years. This figure was significantly lower than the mean age of 13.9 years observed in the goitrous group. The mean age was lowest for thyroid grade 0 and highest for thyroid grades 1b and above. The mean age in high prevalence areas was significantly higher both among goitrous and nongoitrous groups, and in different areas of prevalence the mean age was higher among the goitrous than the nongoitrous. These findings strongly suggest a delay in sexual maturation among girls living in endemic goitre areas and among girls with evidence of goitre.

Geographic Differences for Delay of Sexual Maturation in Peromyscus Leucopus: Effects of Photoperiod, Pinealectomy, and Melatonin1

Effects of short-day photoperiod, pinealectomy, and melatonin on sexual maturation were tested in Peromyscus leucopus from either Connecticut (CT) or Georgia (GA). Laboratory reared-stocks from CT and GA were exposed to short daylength (photoperiod) from birth or 25 days of age. At 12 wk of age, delay in sexual maturation was indicated in most CT mice by decreased testis length, combined testes weight, and seminal vesicle weight. Conversely, GA animals did not delay sexual maturation when exposed to short-day photoperiod from either birth or 25 days of age. These results indicate that responses to short daylengths differ for juvenile CT and GA populations. In a second experiment, pinealectomized or sham-operated CT males were exposed to short-day (9L:15D) or long-day (16L:8D) photoperiod from birth. Pinealectomy blocked the effect of short daylength on reproduction. Therefore, the pineal must be involved in the delay of sexual maturation observed for short-day CT mice. The effects of melatonin, a pineal gland hormone, were tested with chronic s.c. implants or daily injections. In CT mice given either melatonin implants or afternoon injections, sexual maturation was delayed. GA mice were insensitive to all melatonin treatments. Further, no differences in circadian organization (phase angle, duration of activity, period under constant dark) between GA and CT animals were apparent. Collectively, these studies indicate that melatonin is involved in the mechanism responsible for delay of sexual maturation in CT mice. Short-day insensitivity of GA Peromyscus leucopus probably results from a deficiency in the melatonin effector pathway and is not due to a disruption of circadian organization.

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.

Effects of neonatal ovarian X-irradiation in the Chinese hamster. I. Correlation between the age of irradiation and the fertility span.

The fertility span between the first and the last estrus was compared among female Chinese hamsters exposed to 1 Gy X-rays on neonatal day 0, 2, 4, 6, 8, 10 and 14. The fertility span changed dramatically according to the age at the time of irradiation. The females irradiated on day 4, 6 and 8 showed a definite delay in sexual maturation and a very early cessation of the estrous cycles, while those irradiated on day 10, 2 and 14 (in this order) showed a much longer, nevertheless significantly shortened, fertility span. Reduction in the number of juvenile oocytes by acute killing was responsible for this shortened reproductive life. The present study indicated again that the sensitivity of the oocytes to the lethal effects of X-rays is unquestionably meiotic stage-dependent.

Acceleration and delay of sexual maturation in female house mice (Mus domesticus) by urinary chemosignals: mixing urine sources in unequal proportions.

Urine from male mice, from estrous female mice, and from pregnant or lactating female mice accelerate first vaginal estrus in females, whereas urine from grouped female mice delays first estrus. Nine experiments were used to test the effects of treatment of young female mice with urinary chemosignals that influence the onset of first estrus using unequal proportions of urine from the different sources. At ratios of 10-20 parts acceleratory chemosignal to 1 part delay chemosignal the acceleratory effect overrides the delay chemosignal, and the mice attain first estrus at earlier ages than controls. Ratios of about 4 to 1 up to 7 to 1 result in mean ages for puberty that are not accelerated or delayed relative to controls. Over a modest range of actual dose amounts of urine, the ratio effects are the same regardless of the actual quantities of urine employed in treating test females.

Acceleration and delay of sexual maturation in female house mice (Mus domesticus) by urinary chemosignals: Mixing urine sources in unequal proportions.

Acceleration and delay of sexual maturation in female house mice (Mus domesticus) by urinary chemosignals: Mixing urine sources in unequal proportions.

Incidence of avian leukosis virus infection in New Zealand poultry flocks

Abstract Madam:-The infection of hens with viruses of the avian leukosis virus (ALV) groups are an economic problem to layer and broiler poultry breeders in most areas of the world. This is because the infection is associated with a delay in sexual maturity, reduced egg production, smaller and thinner eggs, reduced body weight and an increase in mortality from causes other than lymphoid leukosis. (1) These viruses are retroviruses and as such have the ability to integrate their viral genome into that of the host cell and cause tumours in various avian tissues. The virus can be vertically inherited when it is integrated into the germ line; this is termed an endogenous virus (e.v.). A more common mode of infection is however horizontal. While the core nucleocapsid protein or group specific (gs) antigen of the virus is common to all ALVs, the antigenic properties of the outer viral envelope are used to divide them up into five subgroups (A-E). It is worth noting that the subgroup E viruses are all endogenous...

Effects of chronic administration of LH releasing hormone on age-dependent activities of testicular 4-ene-5α-reductase and 17β-ol-dehydrogenase in mice

Male (WB × C57BL/6)F 1 hybrid mice of 16, 26 and 66 days of age. 4 in each group, were injected daily with 0.2 μg/10 g body weight of LH releasing hormone (LHRH) or saline for 14 days. Testieular homogenates were incubated with [ 14C]4-androstene-3.17-dione and enzyme activities were examined. In mice treated with saline, testicular 17β-ol-dehydrogenase activity increased with age but 4-ene-5α-reductase (5α-reductase) activity decreased with age. LHRH treatment for 14 days starting from day 26 resulted in a delay in sexual maturation, as evidence by significant decreases ( P < 0.05) in seminal vesicle weight and testicular 17β-ol-dehydrogenase activity and by a significant increase ( P < 0.05) in 5α-reduetase activity. However, LHRH treatment starting from day 66 had no significant effect on these testicular enzyme activities.

Hypothalamic-pituitary dysfunction in primary empty sella syndrome in childhood

In a series of 37 consecutive CT scans performed in children referred to our pediatric endocrine unit, an empty (eight) or partially empty (one) sella turcica was found in nine (24%) patients with short stature or delay in sexual maturation, precocious puberty, or hypoparathyroidism. The size and contour of the sella were abnormal in only three patients. Five of the nine children had evidence of decreased growth hormone secretion as determined by subnormal GH secretory responses to provocative tests (peak GH concentration less than 7 ng/ml) or assessment of endogenous 24-hour GH secretion (mean 24-hour GH concentration less than 3 ng/ml). Two children had multiple pituitary hormone deficiencies. Although primary empty sella syndrome was often associated with hypothalamic-pituitary dysfunction in this series, the prevalence of an empty sella in normal children is unknown. Further identification and evaluation of children with empty sella may provide new information regarding the cause of pituitary dysfunction in childhood.

Effect of Photoperiod on Quail Processing Yields

Abstract Bobwhite quail were grown on a 14-hr photophase and Coturnix quail on 8, 10, 14, and 24-hr photophases to analyze the effects of lighting regimen and feed and water withdrawal on carcass weights and processing yields. Eight-week-old Coturnix grown on restricted light regimens had heavier carcasses and greater yields than the Coturnix grown on nonrestrictive light programs. The Coturnix that were grown on restricted light for 8 wk were almost as heavy as the Bobwhite grown for 16 wk. The increase in weight of the Coturnix carcasses was attributed to the delay in sexual maturity. Feed and water deprivation prior to processing resulted in a weight loss of .4%/hr during holding. Concomitant with this increase in shrink was a decrease in yield. Yield decreased at a rate of .15%/hr during the holding times studied.

A follow-up study of the effects of early malnutrition on subsequent development. I. Physical growth and sexual maturation during adolescence.

A follow-up study of growth and development was conducted on 216 Barbadian children aged 9 to 15 yr, half of whom had histories of moderate to severe protein-energy malnutrition in their 1st yr of life. Although index girls had significant delays in sexual maturation and were reduced relative to comparison girls on measures of weight for height, arm circumference, and skinfold thickness, their rate of growth when compared with values obtained 4 yr earlier was equal to or better than that of the comparison group. In contrast, boys in the index group were slightly reduced in height compared with their matched comparisons and had similar patterns of growth and sexual maturation. This study suggests a relationship between an episode of infantile malnutrition and impaired endocrine functioning among girls in the adolescent years.

Bromoergocryptine decreases serum prolactin and delays sexual maturation in male golden hamsters.

The role of prolactin during sexual maturation in male golden hamsters was studied. Controls (n = 23) received vehicle and treated animals (n = 23) received 500 micrograms 2-bromo-alpha-ergocryptine (CB154) daily from 10 days of age until 4 or 5 wk of age. Serum prolactin in prepubertal male hamsters was reduced to a nondetectable level by treatment with the dopamine agonist CB154. Flank gland diameter, body weight, testicular and total accessory sex organ weights, and serum testosterone were all significantly lower (P less than 0.05) in the CB154-treated animals. In addition, seminiferous tubule area, seminiferous tubule luminal and cellular areas, and number of late spermatids per tubule cross-section were significantly reduced (P less than 0.01) in CB154-treated prepubertal males. Thus, the absence of prolactin retarded sexual maturation in male golden hamsters. These data suggest, that prolactin enhances testosterone production during the process of sexual maturation and supports the development of androgen-dependent tissues.