Ontogeny of pulsatile gonadotrophin secretion and pituitary responsiveness in male puberty in man: a mixed longitudinal and cross-sectional study

1989 ◽  
Vol 123 (2) ◽  
pp. 347-359 ◽  
Author(s):  
F. C. W. Wu ◽  
S. M. Borrow ◽  
K. Nicol ◽  
R. Elton ◽  
W. M. Hunter

ABSTRACT The onset of puberty is characterized by a sleep-associated increase in pulsatile LH secretion which is not observed in adults. The ontogeny of gonadotrophin secretion during pubertal maturation may reflect changes in endogenous LHRH secretion, pituitary sensitivity to LHRH and/or alterations in gonadal steroid feedback. To understand the interplay between these mechanisms, we have examined the pulsatile pattern of plasma LH, FSH, testosterone, oestradiol and prolactin between 20.00 and 09.00 h and the pituitary response to repeated exogenous LHRH stimulation in 16 boys with delayed puberty (age 16·3±2·7 (s.e.m.) years) on one to four occasions in a mixed longitudinal/cross-sectional analysis. Physical maturity was determined by Tanner G staging (1–5) and clinical progress followed for a mean duration of 22·4 ± 8·5 months during which 33 hormone profiles were obtained. Nocturnal (23.00–09.00 h) LH pulse frequency increased to a peak of 0·54±0·03/h at stage 2 which was followed by a gradual decline to 0·42 ± 0·04/h at stage 5. The appearance of LH pulses in the evening (20.00–23.00 h), probably representative of the rest of the day, was delayed until mid-puberty from which point frequency increased to a peak of 0·53 ±0·08/h at stage 5. LH pulse amplitude showed a linear increase from stages 1 to 5, with nocturnal pulse amplitudes being higher than evening pulses throughout. FSH did not show a clear pulsatile pattern. The LH: FSH ratio reversed from < 1 to > 1 at stage 2. The LH response to exogenous LHRH increased in parallel with LH pulse amplitude. There was no difference in the pattern of LH response to repeated LHRH stimulation as puberty advanced; the first stimulus always elicited a greater response than subsequent doses. In contrast, the FSH response to LHRH was maximal at stage 1 and became attenuated thereafter. The estimated mean nocturnal LHRH concentration or amplitude did not show any increase during pubertal maturation from 20·42±11·57 at stage 1 to 35·96 ± 20·83 ng/l at stage 5. In conclusion, the sequential changes in this study suggest that the sleep-entrained increase in LHRH pulse frequency plays a key role at the onset of puberty. By enhancing pituitary responsiveness and setting in motion a cascade of events, this peripubertal augmentation of LHRH pulse frequency can account for most of the subsequent changes in LH, FSH and testosterone secretion during pubertal development in the male without any apparent alteration in LHRH pulse amplitude. Journal of Endocrinology (1989) 123, 347–359

Endocrinology ◽  
2001 ◽  
Vol 142 (7) ◽  
pp. 2929-2936 ◽  
Author(s):  
Cheryl L. Sisk ◽  
Heather N. Richardson ◽  
Patrick E. Chappell ◽  
Jon E. Levine

Abstract Pubertal development in female rats is characterized by increased LH levels and the appearance of estrogen-dependent afternoon LH mini-surges. In these studies we performed the first analysis of GnRH patterns in peripubertal rats to determine whether there are similar changes in pulsatile GnRH release. Microdialysis samples were collected at 5-min intervals throughout a 5-h afternoon period from 22 rats sampled on a single day between 30–47 days of age. Adult female rats were sampled on proestrus for comparison. In 30- to 33-day-old rats, GnRH release was infrequent (2.7 pulses/5 h; n = 3), whereas intermediate pulse frequencies were observed in 34- to 37-day-old rats (6.4 pulses/5 h; n = 9) and 38- to 42-day-old (5.0 pulses/5 h; n = 5) rats. The highest GnRH pulse frequencies were observed in 43- to 47-day-old rats (9.4 pulses/5 h; n = 5). Mean GnRH pulse amplitude did not vary significantly with age. Animals sampled before vaginal opening (VO) exhibited significantly slower GnRH pulse frequencies than those sampled after vaginal opening (1.3 pulses/5 h pre-VO vs. 7.6 pulses/5 h post-VO; P= 0.01). An afternoon increase in GnRH secretion, defined operationally as a greater than 25% increase in mean GnRH levels in the last half of the sampling period and tentatively termed a mini-surge, was observed in 0%, 33%, 40%, and 60% of 30- to 33-, 34- to 37-, 38- to 42-, and 43- to 47-day-old rats, respectively. An overall increase in GnRH pulse frequency was observed in females displaying a mini-surge (9.0 pulses/5 h with mini-surge compared with 4.7 pulses/5 h with no mini-surge). The mini-surge itself, however, was associated with a late afternoon increase in GnRH pulse amplitude and not in pulse frequency. In adult proestrous rats, peak levels during the GnRH surge were an order of magnitude greater than those reached in pubertal animals. Our findings demonstrate that pubertal maturation in the female rat is associated with an acceleration of GnRH pulse generator activity and that later stages of pubertal maturation are characterized by the appearance of afternoon increases in GnRH release that may underlie previously reported mini-surges in LH.


Medicina ◽  
2020 ◽  
Vol 57 (1) ◽  
pp. 15
Author(s):  
Altynay Balmukhanova ◽  
Kairat Kabulbayev ◽  
Harika Alpay ◽  
Assiya Kanatbayeva ◽  
Aigul Balmukhanova

Background and objectives: Chronic kidney disease (CKD) in children is a complex medical and social issue around the world. One of the serious complications is mineral-bone disorder (CKD-MBD) which might determine the prognosis of patients and their quality of life. Fibroblast growth factor 23 (FGF-23) is a phosphaturic hormone which is involved in the pathogenesis of CKD-MBD. The purpose of the study was to determine what comes first in children with CKD: FGF-23 or phosphate. Materials and Methods: This cross-sectional study included 73 children aged 2–18 years with CKD stages 1–5. We measured FGF-23 and other bone markers in blood samples and studied their associations. Results: Early elevations of FGF-23 were identified in children with CKD stage 2 compared with stage 1 (1.6 (1.5–1.8) pmol/L versus 0.65 (0.22–1.08), p = 0.029). There were significant differences between the advanced stages of the disease. FGF-23 correlated with PTH (r = 0.807, p = 0.000) and phosphate (r = 0.473, p = 0.000). Our study revealed that the elevated level of FGF-23 went ahead hyperphosphatemia and elevated PTH. Thus, more than 50% of children with CKD stage 2 had the elevating level of serum FGF-23, and that index became increasing with the disease progression and it achieved 100% at the dialysis stage. The serum phosphate increased more slowly and only 70.6% of children with CKD stage 5 had the increased values. The PTH increase was more dynamic. Conclusions: FGF-23 is an essential biomarker, elevates long before other markers of bone metabolism (phosphate), and might represent a clinical course of disease.


Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 163-171 ◽  
Author(s):  
Glenn C. Harris ◽  
Jon E. Levine

Abstract A microdialysis technique was used in male rats to directly assess the postulate that pubertal maturation is associated with accelerated GnRH pulsatility. Juvenile male rats, postnatal d 43 or 45 (n = 4) were stereotaxically fitted with guide cannulas directed toward the lateral median eminence, and repeated microdialysis experiments were conducted over 4–6 d. In each session, samples were collected continuously over 12 h (0900–2100 h) at 5-min intervals Results from individual peripubertal animals were pooled into two time bins for postnatal d 45–47 and 48–50, respectively, and GnRH characteristics were compared between the two epochs. The GnRH pulse frequency and mean GnRH concentration were significantly elevated at 48–50 d compared with 45–47 d. The GnRH pulsatility characteristics for 45–47 d vs. 48–50 d were as follows: pulse frequency, 0.74 ± 0.16 vs. 1.79 ± 0.19 pulses/h (P &lt; 0.05); pulse amplitude, 254.1 ± 22.3 vs. 347.2 ± 15.8 Δpg/ml (difference in value from trough to peak); and mean release, 0.55 ± 0.03 vs. 2.04 ± 0.04 pg/5 min (P &lt; 0.05). An additional two rats were dialyzed only once on postnatal d 50 to assess the effects of repeated sampling; the GnRH pulse characteristics in these animals were similar to those in rats sampled for a third or fourth time on postnatal d 48–50. To further assess the possible effects of repeated sampling on GnRH release profiles, a group of adult male rats (postnatal d 95–105; n = 3) was also dialyzed on four consecutive days. In these rats no significant alteration in GnRH pulse generator activity was observed over the four sessions. Moreover, the increase in GnRH pulse frequency observed in the peripubertal rats was found to be sustained in adult animals. To better understand the temporal relationship of GnRH pulse generator activity to reproductive maturation, groups of male rats were killed from postnatal d 45–56 along with an adult group at 95–105 d (n = 5/group) and examined for physiological signs of reproductive development. Gradual increases in serum levels of LH and testosterone and decreases in FSH and inhibin B were seen from postnatal d 45–56 to adulthood. Mature spermatozoa were found in the vas deferens by postnatal d 53. Our results demonstrate that in the late juvenile stage of male rat development, GnRH pulse generator activity is gradually accelerated over the course of consecutive days. This acceleration occurs over a period during which serum LH and testosterone are rising to adult levels, and it precedes the presence of mature spermatozoa in the vas deferens by 3 d. Our observations provide direct support for the hypothesis that an acceleration of GnRH pulsatility is the critical neural stimulus for the initiation of pubertal maturation in males. The peripheral and central cues that prompt the pubertal activation of the GnRH pulse generator remain to be characterized.


Author(s):  
Nandini Vijayakanthi ◽  
David J Marcus ◽  
Sobha P Fritz ◽  
Yijin Xiang ◽  
Doris Fadoju

Abstract Objectives Delayed puberty & short stature in girls with Turner syndrome(TS) can lead to low body image, self-esteem & satisfaction. We aimed to evaluate body image, self-perception, and satisfaction among girls with TS using Multi-Dimensional Body Image Self Relations Questionnaire -Appearance Scale (MBSRQ-AS). Methods Patients with karyotype-proven diagnosis of TS between 15-21 years were included after they achieved final adult height. We used MBSRQ-AS instrument with 5 sub-scales: Appearance Evaluation(AE), Appearance Orientation(AO), Body Areas Satisfaction Scale(BASS), Overweight Preoccupation(OWP) and Self Classified Weight(SCW) sub-scales. Mean scores were compared to available sex matched population norms & compared between different sub-cohorts. Results Of 59 eligible girls, 37 girls agreed to participate with mean age : 17.35 ±1.6 years. Turner girls had significantly lower scores compared to sex-matched population norms in AO [mean(SD): 3.32(0.42) vs 3.91(0.6)]; (p&lt;0.001) and SCW [mean(SD): 3.26(0.71) vs 3.57(0.73); (p=0.01)] sub-scales. In contrast, they had slightly higher scores in BASS [ mean(SD): 3.38(0.74) vs 3.23(0.74); (p=0.23)] & OWP [mean(SD): 3.12(0.39) vs 3.03(0.96); (p=0.21)] sub-scales though not statistically significant. Girls with classic 45 X karyotype and those who were overweight/obese had lower scores in AE & AO sub-scales compared to normal population (p&lt;0.05). Conclusion Compared to sex-matched population norms, Turner girls are not reporting negative effects due to their appearance & report general satisfaction with most areas of their body; however, Turner girls with classic karyotype or who were obese/overweight were generally unhappy with their physical appearance. They also seem to not focus their attention on their appearance.


2014 ◽  
Vol 2014 ◽  
pp. 1-6
Author(s):  
Pratik Gahalaut ◽  
Nitin Mishra ◽  
Sandhya Chauhan ◽  
Mir Mubashir Ali ◽  
Madhur Kant Rastogi ◽  
...  

Lunula is the white, half-moon shaped area seen in proximal ends of some nails. Though a few studies have described the nail changes that can occur in association with HIV infection, none of these paid much attention to lunula. Aims and Objectives. To study the lunula in fingernails among HIV infected patients. Materials and Methods. An observational, cross-sectional study to record presence of lunula in 168 HIV-positive patients and compare it with age and sex matched 168 healthy HIV-negative control. Anolunula (absence of lunula) in HIV-positive patients was correlated with CD4 counts, stages of HIV infection, time since patient was diagnosed as HIV-positive, and status of antiretroviral therapy. Results. Anolunula was present in significantly more fingernails in HIV-positive patients compared to HIV-negative controls. There was a highly significant difference for total anolunula (anolunula in all fingernails) in study and control group. Incidence of total anolunula was directly proportional to the stage of HIV infection, increasing progressively as the HIV infection advances from stage 1 to stage 4. Conclusion. Absence of lunula is related to not only HIV infection per se but also the stages of HIV infection.


2018 ◽  
Vol 3 (1) ◽  
pp. 273-283 ◽  
Author(s):  
Jian-Jun Liu ◽  
Sylvia Liu ◽  
Resham L Gurung ◽  
Clara Chan ◽  
Keven Ang ◽  
...  

Abstract Background and Aim The kidney is the main site for glucagon clearance. However, a recent study showed that hyperglucagonemia in patients with end-stage renal disease might not be caused by full-length intact glucagon. Additionally, the relationship between glucagon and renal function in early-stage chronic kidney disease (CKD) has not yet been characterized. We studied the association of fasting glucagon with renal function across a wide range of glomerular filtration rates (GFRs) in participants with type 2 diabetes. Participants and Methods 326 participants with type 2 diabetes and renal function spanning CKD stage 1 to 5 were included in the present cross-sectional study. Fasting full-length plasma glucagon was quantified using a newly developed ELISA (Mercodia AB, Uppsala, Sweden). Results The fasting plasma glucagon level was elevated linearly from CKD stage 1 to 5 [from a median of 2.5 pM (interquartile range, 1.4 to 4.7) in CKD 1 to a median of 8.3 pM (interquartile range, 5.9 to 12.8) in CKD 5; P for trend &lt; 0.0001], from as early as CKD stage 2 compared with that in stage 1 (Bonferroni-corrected P &lt; 0.0001). The estimated GFR and homeostatic model of assessment–insulin resistance were the main determinants of the fasting glucagon level. These explained 14.3% and 10.3% of the glucagon variance, respectively. Albuminuria was not associated with fasting glucagon after adjustment for estimated GFR. Conclusions Fasting full-length glucagon was elevated linearly with the deterioration in renal function in individuals with type 2 diabetes, even in those with early CKD. In addition to renal function, insulin sensitivity was also a main determinant of glucagon variance.


1989 ◽  
Vol 121 (2) ◽  
pp. 383-387 ◽  
Author(s):  
J. M. P. Holly ◽  
C. P. Smith ◽  
D. B. Dunger ◽  
J. A. Edge ◽  
R. A. Biddlecombe ◽  
...  

ABSTRACT We have looked at the relationship between fasting levels of insulin and a small insulin-like growth factor (IGF)-binding protein (IBP-1) in a cross-sectional study of 116 normal subjects aged 5–48 years. The relationship between IBP-1 and insulin was also examined within individual normal children in over-night profiles of IBP-1 and insulin obtained from two children at each stage of puberty (Tanner stages 1–5). In the cross-sectional study high levels of IBP-1 were found in early childhood and these fell throughout puberty as fasting levels of insulin rose. Multiple regression analysis revealed that both these changes were predominantly due to pubertal development rather than to age. After the age of 16 IBP-1 levels remained low despite fasting insulin levels returning to prepubertal levels. A strong negative correlation was obtained between IBP-1 and insulin in children of 5–16 years (r = −0·63; n = 60; P <0·001), no such relationship being found after the age of 16. In the second study, IBP-1 underwent a marked circadian variation in all cases and an inverse correlation with insulin, measured at the same time, was obtained at pubertal stages 1 to 4, but not at stage 5 (pooled data stages 1–4, r = −0·69; n = 53; P <0·001). We have demonstrated that a potential inhibitor of IGF-activity is inversely related to insulin throughout the period of active GH-related growth and that this relationship weakens after puberty. Journal of Endocrinology (1989) 121, 383–387


2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Maohua Miao ◽  
Ziliang Wang ◽  
Xiaoqin Liu ◽  
Hong Liang ◽  
Zhijun Zhou ◽  
...  

2018 ◽  
Vol 13 (3) ◽  
pp. 463-469 ◽  
Author(s):  
Shaji C. Menon ◽  
Ragheed Al-Dulaimi ◽  
Brian W. McCrindle ◽  
David J. Goldberg ◽  
Ritu Sachdeva ◽  
...  

Neurology ◽  
2019 ◽  
Vol 93 (10) ◽  
pp. e984-e994 ◽  
Author(s):  
Adriano Chiò ◽  
Cristina Moglia ◽  
Antonio Canosa ◽  
Umberto Manera ◽  
Rosario Vasta ◽  
...  

ObjectiveTo assess the association of the degree of severity of motor impairment to that of cognitive impairment in a large cohort of patients with amyotrophic lateral sclerosis (ALS).MethodsThis is a population-based cross-sectional study on patients with ALS incident in Piemonte, Italy, between 2007 and 2015. Cognitive status was classified according to the revised ALS–FTD Consensus Criteria. The King system and the Milano Torino Staging system (MiToS) were used for defining the severity of motor impairment.ResultsOf the 797 patients included in the study, 163 (20.5%) had ALS–frontotemporal dementia (FTD), 38 (4.8%) cognitive and behavioral impairment (ALScbi), 132 (16.6%) cognitive impairment (ALSci), 63 (7.9%) behavioral impairment (ALSbi), 16 (2.0%) nonexecutive impairment, and 385 (48.2%) were cognitively normal. According to King staging, the frequency of cases with ALS-FTD progressively increased from 16.5% in stage 1–44.4% in stage 4; conversely, the frequency of ALSci, ALSbi, and ALScbi increased from King stage 1 to King stage 3 and decreased thereafter. A similar pattern was observed with the MiToS staging. ALS-FTD was more frequent in patients with bulbar involvement at time of cognitive testing. Patients with C9ORF72 expansion (n = 61) showed more severe cognitive impairment with increasing King and MiToS stages.ConclusionOur findings suggest that ALS motor and cognitive components may worsen in parallel, and that cognitive impairment becomes more pronounced when bulbar function is involved. Our data support the hypothesis that ALS pathology disseminates in a regional ordered sequence, through a cortico-efferent spreading model.


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