Adrenomedullin: new inhibitory regulator for cortisol synthesis and secretion

2021 ◽  
Author(s):  
Simon Travers ◽  
Laetitia Martinerie ◽  
Qiong-Yao Xue ◽  
Julie Perrot ◽  
Say Viengchareun ◽  
...  

Preterm birth is associated with immaturity of several crucial physiological functions notably those prevailing in lung and kidney. Recently, a steroid secretion deficiency was identified in very preterm neonates, associated with a partial yet transient deficiency in 11β-hydroxylase activity, sustaining cortisol synthesis. However, the P450c11β enzyme is expressed in preterm adrenal glands, so we hypothesized an inhibition of cortisol production by adrenomedullin (ADM), a peptide highly produced in neonates and whose effect on steroidogenesis remains poorly known. We studied effects of ADM on three models: 104 cord-blood samples of the PREMALDO neonate cohort, genetically targeted mice overexpressing ADM and two human adrenocortical cell lines (H295R and HAC15 cells). Mid-regional-proADM (MR-proADM) quantification in cord-blood samples showed strong negative correlation with gestational age (P=0.0004), cortisol production (P<0.0001) and 11β-hydroxylase activity index (P<0.0001). Mean MR-proADM was higher in very preterm than in term neonates (1.12 vs. 0.60 nmol/L, P<0.0001). ADM-overexpression mice revealed lower 11β-hydroxylase activity index (P<0.05). Otherwise, aldosterone levels measured by LC-MS/MS were higher in ADM-overexpression mice (0.83 vs. 0.46 ng/mL, P<0.05). More importantly, the negative relationship between adrenal ADM expression and aldosterone production found in control was lacking in the ADM-overexpression mice. Finally, LC-MS/MS and gene expression studies on H295R and HAC15 cells revealed an ADM-induced inhibition of both cortisol secretion in cell supernatants and CYP11B1 expression. Collectively, our results converge towards an inhibitory effect of ADM on glucocorticoid synthesis in humans and should be considered to explain the steroid secretion deficiency observed at birth in premature newborns.

2020 ◽  
Vol 58 (4) ◽  
pp. e113-e116
Author(s):  
Serena Valsami ◽  
Maria Kollia ◽  
Vasiliki Mougiou ◽  
Rozeta Sokou ◽  
Elina Isaakidou ◽  
...  

2015 ◽  
Vol 46 (S 01) ◽  
Author(s):  
M. Cremer ◽  
K. Jost ◽  
S. Schulzke ◽  
P. Weber ◽  
A. Datta

2015 ◽  
Vol 2 (11) ◽  
Author(s):  
Phuc Van Pham ◽  
Binh Thanh Vu ◽  
Viet Quoc Pham ◽  
Phong Minh Le ◽  
Hanh Thi Le ◽  
...  

1995 ◽  
Vol 145 (3) ◽  
pp. 479-490 ◽  
Author(s):  
B K Campbell ◽  
B M Gordon ◽  
C G Tsonis ◽  
R J Scaramuzzi

Abstract Ewes with ovarian autotransplants received either inhibin antiserum (10 ml i.v. raised in sheep against recombinant 32 kDa human inhibin; n=6) or sheep serum (10 ml i.v.; n=5) on day 3 of the luteal phase with additional daily injections (1 ml i.v.) from 48 h after the initial bolus until day 13. Jugular and ovarian venous blood samples were taken 4-hourly over days 2–13 of the luteal phase. Blood samples were also taken at more frequent intervals (every 10–15 min for 2–3 h) to examine pulsatile secretory responses from the ovary to endogenous and gonadotrophin-releasing hormone-induced (150 ng i.m.) LH pulses on days 4, 6, 8, 10 and 12 of the luteal phase. Plasma FSH levels, ovarian steroid secretion and ovarian follicular development were measured. The ovarian follicle population was estimated daily by real time ultrasound scanning. Immunisation against inhibin resulted in a 3- to 4-fold increase (P<0·001) in plasma FSH levels within 8 h with levels remaining elevated over controls for 6–7 days. Within 24 h of immunisation there was an increase in the number of small ovarian follicles (P<0·05) and by 3 days after treatment immunised ewes had 4–6 large ovarian follicles/ewe with this increase in the total number of large follicles being maintained for the rest of the experimental period (P<0·05). Mean ovarian oestradiol secretion during intensive bleeds was not different from controls 24 h after immunisation, but by 3 days after immunisation it was elevated 4- to 5-fold (P<0·001) over controls with this increase being maintained throughout the experiment. Similar responses to immunisation against inhibin in androstenedione secretion were observed although mean androstenedione secretion was not elevated until 7 days after treatment. In vitro antibody titres in immunised ewes remained elevated but declined steadily (P<0·001) over the experimental period. We conclude that the initial stimulation of follicle development and ovarian steroid secretion following passive immunisation against inhibin can be attributed to increased blood FSH. However, the fact that with time FSH declined but increased follicle development was sustained, despite maintenance of high circulating antibody titres, suggests that on a longer term basis inhibin immunisation may stimulate ovarian function by interfering with the modulation of follicle development by inhibin at an ovarian level. Journal of Endocrinology (1995) 145, 479–490


PEDIATRICS ◽  
1993 ◽  
Vol 91 (1) ◽  
pp. 88-91
Author(s):  
Rakesh S. Chhabra ◽  
Luc P. Brion ◽  
Martha Castro ◽  
Lawrence Freundlich ◽  
Joy H. Glaser

The incidence of congenital syphilis has increased rapidly over the past few years. Most infected mothers and their newborns are asymptomatic at birth and diagnosis depends on serologic testing during pregnancy and at delivery. This study was initiated to compare maternal sera, cord blood, and neonatal sera for detecting presumptive congenital syphilis and to assess the role of maternal treatment (administration of penicillin to the mother at least 1 month before delivery) on the serologic results at the time of delivery. The serologic results from all live deliveries complicated by a positive maternal and/or neonatal test for syphilis during a 12-month period were compared using χ2 analysis and multiple comparisons for proportions. Of 3306 livebirths, 73 (2.2%) were complicated by a positive maternal or neonatal serology. At delivery, the serologic test was positive in 68 (94%) of 72 maternal sera, 30 (50%) of 60 cord sera, and 43 (63%) of 68 neonatal sera. In the absence of maternal treatment, 95% of the maternal sera, 66% of the cord blood samples, and 86% of the neonatal sera were positive. If the mother had been treated, 94% of maternal sera, 36% of cord sera, and 39% of neonatal sera were positive. Cord blood and neonatal sera appear to be inferior to maternal sera for detecting prenatal exposure to syphilis. Cord serology is also inferior to neonatal serology at 2 to 3 days of age. The most effective way to identify newborns at risk for congenital syphilis is to obtain a maternal serologic diagnosis during pregnancy and to test maternal and neonatal sera at delivery.


PEDIATRICS ◽  
1962 ◽  
Vol 29 (3) ◽  
pp. 369-375
Author(s):  
William M. Michener ◽  
W. Newlon Tauxe ◽  
Alvin B. Hayles

Normal values for the measurement of thyroidal function using the erythrocytic uptake of I131-labeled triiodothyronine and the thyroxine-binding capacity of the inter-alpha globulin were established. Paired maternal and cord blood samples collected at the time of delivery were studied with these methods. The erythrocytic uptake of labeled hormone was increased in cord blood as compared to maternal blood. Cord blood apparently binds exogenous triiodothyronine in a different manner than it does exogenous thyroxine. Whether this is a qualitative or quantitative difference was not shown in this study.


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