analyses Data are reported as the least squares means± s.e.m . Analysis of variance (ANOVA) was used to compare means in the ontogeny experiment and the treatment effects of MMI injections (SAS version 8.02, PROC GLM or PROC MIXED procedures, SAS
Michael Muchow, Ioannis Bossis and Tom E Porter
Kok Lim Kua, Shanming Hu, Chunlin Wang, Jianrong Yao, Diana Dang, Alexander B Sawatzke, Jeffrey L Segar, Kai Wang and Andrew W Norris
skeletal muscle. However, fetal insulin signaling in skeletal muscle has received little experimental attention ( Anand et al. 2002 , Dunlop et al. 2015 ) such that even the molecular ontogeny of fetal insulin signaling is not well characterized
T. Sokka and I. Huhtaniemi
The sequence of appearance of FSH and LH receptors, and response of cyclic AMP (cAMP) production to these hormones and cholera toxin, were studied in the fetal and neonatal rat ovary. Specific binding of radio-labelled human (h)FSH and chorionic gonadotrophin (CG) to ovarian homogenates was first detectable on day 7 of life. The content of FSH receptors per ovary increased tenfold between days 7 and 16, and that of LH receptors 27-fold. A significant response of cAMP production in vitro to FSH appeared on day 4 of life, but no significant effect of hCG on cAMP was achieved until day 7. In contrast, cholera toxin had a marked effect on cAMP production by day 17 of fetal life. Although both FSH and LH receptors were detectable in the neonatal rat ovary by day 7, the present findings indicate that the FSH responsiveness of the ovary appears earlier than that of LH. The post-receptor machinery of cAMP production is already functional in the fetal ovary as shown by the experiments with cholera toxin. The appearance of the receptor may therefore be the last link in the ontogeny of the gonadotrophin signal transduction system in the ovary. To study the hormone dependence of the appearance of gonadotrophin responsiveness, neonatal female rats were treated on days 1–6 or 1–9 of life with a potent gonadotrophin-releasing hormone antagonist, and killed on the following day. In both treatment groups, the pituitary LH and FSH contents were suppressed. The body weights remained unaltered, but ovarian weights decreased significantly during both periods of treatment (days 1–6,26·1%, P < 0·05; days 1–9,54·0%, P <0·001). No difference in basal or FSH-stimulated cAMP production was achieved by antagonist treatment for the first 6 days of life. The basal and hCG-stimulated rates of cAMP production per ovary were reduced in animals treated for 9 days (P <0·01), but the FSH-stimulated cAMP production remained unaffected. Hence, whereas the responsiveness to FSH seems to develop in the absence of normal gonadotrophin secretion, a causal relationship between normal gonadotrophin levels and the appearance of LH/hCG responsiveness is apparent in the neonatal rat ovary.
Journal of Endocrinology (1990) 127, 297–303
R. J. Johnson, J. P. McMurtry and F. J. Ballard
The ontogeny and secretory pattern of plasma insulin-like growth factor-I (IGF-I) in relation to GH secretion were studied in meat-type (broiler) poultry during prepubertal and post-pubertal growth. Male and female broiler chickens of two commercial strains (strains A and B) were reared from 1 to 198 days of age. From 1 to 49 days of age birds were reared in raised-wire cages and thereafter in deep-litter pens, with food available ad libitum. Blood samples were taken at regular intervals during growth, and at 29 and 43 days of age representative birds were cannulated and serial blood samples taken at 10-min intervals for 5 to 7 h. Plasma concentrations of GH and IGF-I were measured by radioimmunoassay.
Birds of strain A were heavier (P<0·05) than those of strain B from 12 to 35 days of age. In general, male birds were heavier (P<0·01) than females from 12 to 35 days of age. Plasma GH concentrations were significantly higher (P<0·05) from 12 to 35 days of age, while plasma IGF-I concentrations were lower (P<0·05) from 6 to 21 days of age in male compared with female birds. Plasma IGF-I concentration increased with age, reaching a plateau at 28 days of age, while plasma GH concentration declined over the same period. Plasma IGF-I concentrations declined in a linear manner from 49 to 198 days of age, and there was no evidence of a pubertal increase. There were no differences between strains in the plasma concentrations of GH or IGF-I. Serial blood sampling at 29 and 43 days of age showed that there was no relationship between GH and IGF-I, despite a highly pulsatile GH secretory pattern which existed at 29 days of age. These results show that as the plasma concentration of GH declines that of IGF-I increases. Plasma concentration of both GH and IGF-I in broiler chickens was sexually dimorphic, especially during the early growth phase to about 35 days of age.
Journal of Endocrinology (1990) 124, 81–87
T A Cudd, M LeBlanc, M Silver, W Norman, J Madison, M Keller-Wood and C E Wood
Fetal maturation and the timing of parturition in both sheep and primates are thought to be controlled by the hypothalamic-pituitary-adrenal axis but little is known about the endocrinology of the equine fetus. We investigated the ontogeny of plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol and corticosteroid binding capacity in the late-gestation fetal horse. We also wished to determine whether there is ultradian rhythmic release of ACTH and cortisol in fetal horses and we compared fetuses to maternal and non-pregnant adult horses. Six fetuses, 278–304 days gestation (term ≈335), were catheterized and sampled daily until delivery. Mean (± s.e.m.) ACTH concentrations increased significantly from 159 ±21 to 246 ±42 pg/ml over the last 2 days before parturition. Fetal cortisol increased significantly from 3·1±1·0 to 13·4±3·7 ng/ml (mean±s.e.m.) over the last 9 days before delivery. The slope of regressions for ACTH and cortisol concentrations with respect to time were positive in all subjects and statistically significant in 3 of 6 for ACTH and 5 of 6 for cortisol. Fetal corticosteroid binding capacity declined from 49·5 ±20·5 to 16·1 ± 2·2 ng/ml (mean ± s.e.m.) over the last 10 days before parturition. However, the greatest changes in ACTH, cortisol and corticosteroid binding capacity occurred very late in gestation, during the last 48 to 72 h before parturition. Significant peaks and nadirs in plasma ACTH concentration were detected in all 20 experiments and in plasma cortisol concentration in 17 of 20 experiments using Cluster analysis. We found statistically significant periods of oscillation between 11 and 64 min in plasma ACTH (19 of 20 experiments) and cortisol (15 of 20 experiments) using power spectral density analysis. Statistically significant periods between 11 and 17 min were detected in 11 of 20 experiments for ACTH and in 8 of 20 for cortisol. We conclude that: 1) at the end of gestation, equine fetal plasma ACTH and cortisol concentrations increase while corticosteroid binding capacity decreases suggesting that there is a disproportionately large increase in unbound cortisol at this time; 2) the secretion of ACTH and cortisol is rhythmic in both fetal and adult horses; 3) most animals exhibit a period of oscillation between 11 and 17 min; and 4) there is no apparent developmental change from late gestation to adulthood in the ultradian oscillator influencing ACTH and cortisol secretion in this species.
Journal of Endocrinology (1995) 144, 271–283
Amy R Quinn, Cynthia L Blanco, Carla Perego, Giovanna Finzi, Stefano La Rosa, Carlo Capella, Rodolfo Guardado-Mendoza, Francesca Casiraghi, Amalia Gastaldelli, Marney Johnson, Edward J Dick Jr and Franco Folli
pancreas development will further our understanding of the disruptive glucose metabolism in these infants. The ontogeny of the endocrine pancreas in the fetal/newborn baboon model provides insight into the normal pancreas development from late gestation
S. Karanth, M. K. Gill, A. Dutt, N. Lehri and H. S. Juneja
The effect of s.c. daily injections of 10 or 1000 ng 5α-dihydrotestosterone (DHT)/100 g body weight from birth to day 21, or from days 26 to 117 of age, on the changes in concentration of serum and pituitary gonadotrophins was investigated in male rats. Treatment with 10 ng DHT from days 1 to 21 depressed serum FSH, but not LH, at day 7, while 1000 ng DHT depressed both serum LH and FSH. Treatment with both doses of DHT reduced pituitary levels of LH and FSH at day 7, with FSH being more depressed than LH. Treatment with 10 ng DHT from days 26 to 117 increased serum FSH from days 82 to 117, while 1000 ng DHT did not have this effect. Treatment with 1000 ng, but not 10 ng, DHT between days 26 and 117 reduced pituitary levels of LH and FSH at day 40. Rats treated with the two doses of DHT from days 26 to 117 showed a difference in the responsiveness of the pituitary to LH-releasing hormone (LHRH). Treatment with 10 ng DHT enhanced LHRH-induced release of LH without affecting FSH release, while 1000 ng DHT depressed LHRH-induced release of FSH but not of LH. These findings support the view that DHT may play a modulatory role in the ontogeny of serum gonadotrophins and the responsiveness of the pituitary to LHRH during the onset of puberty in the male rat.
J. Endocr. (1986) 108, 369–375
D. R. Shamley, R. Buffenstein, G. Veale and J. M. Pettifor
The effects of vitamin D3 deficiency on the ontogeny of calcium-binding proteins (CaBPs) and the vitamin D receptor in the duodenum, kidney and cerebellum of the mouse were examined. Maternal vitamin D status did not affect the time of appearance of the fetal 28 kDa CaBP (CaBP-D28k) in the cerebellum, kidney and duodenum, and the 9 kDa CaBP (CaBP-D9k) in the intestine and kidney. Vitamin D receptor was undetectable in all fetal tissues, regardless of maternal vitamin D status, at all stages of gestation examined. Thus it appears that maternal vitamin D status does not affect the ontogeny of CaBP-D9k or CaBP-D28k in the mouse fetus. The factors that influence the appearance of calbindins in the fetus are unclear.
Journal of Endocrinology (1993) 139, 473–478
HJ Speirs, Seckl JR and RW Brown
Glucocorticoids play important roles in organ development and 'fetal programming'. Fetal exposure to excess glucocorticoids reduces birth weight and causes later hypertension. To investigate these processes further we have determined the detailed ontogeny in the mouse of the glucocorticoid receptor (GR) and 11beta-hydroxysteroid dehydrogenase type-1 (11beta-HSD1), which amplifies glucocorticoid levels locally; the ontogeny was determined using in situ hybridisation from embryonic day 9.5 (E9.5, term=E19) until after birth. At E9.5 fetal GR mRNA levels are very low, except in fetal placenta. GR gene expression rises during gestation with striking tissue-specific differences in timing and extent. Before E13.5, an increase is clear in gastrointestinal (GI) and upper respiratory tracts, discrete central nervous system (CNS) regions, precartilage and especially in the liver (E10.5-E12). Later, further increases occur in lung, GI and upper respiratory tracts, muscle, pituitary and thymus. In a few tissues such increases are temporary, e.g. ureteric ducts (E13.5-E16.5) and pancreas (E14.5-E16.5, expression later falling sharply). Fetal 11beta-HSD1 mRNA expression is first clearly observed at E14.5-E15, initially in the fetal placenta then in the umbilical cord. Later, 11beta-HSD1 expression is seen as follows: (i) from E15 in lung and liver, rising strongly; (ii) thymus, from E15 (lower level); (iii) at low levels in a few brain regions, including the hippocampus (E16.5+); and (iv) in muscle group fascial planes and tendon insertions. This is the first detailed study of the ontogeny of these two genes and, in combination with previous work on the ontogeny of 11beta-HSD2 and the mineralocorticoid receptor, suggests potential critical periods of glucocorticoid sensitivity during development for several organ systems.
F. C. W. Wu, S. M. Borrow, K. Nicol, R. Elton and W. M. Hunter
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