Increase in milk secretion and mammary blood flow by intra-arterial infusion of insulin-like growth factor-I into the mammary gland of the goat

1990 ◽  
Vol 126 (3) ◽  
pp. 437-443 ◽  
Author(s):  
C. G. Prosser ◽  
I. R. Fleet ◽  
A. N. Corps ◽  
E. R. Froesch ◽  
R. B. Heap

ABSTRACT The close-arterial infusion of free insulin-like growth factor-I (IGF-I; 1·1 nmol/min) for 6 h into the pudic artery supplying one mammary gland of lactating goats caused a 25±6% (mean ± s.e.m., n = 6) increase in the rate of milk secretion of that gland. The increase in the rate of milk secretion in the adjacent non-infused gland (14±4%) was not significantly different from that observed during saline infusion (4±5%). Blood flow to the infused gland was increased from 378±26 ml/min 1 h before to 487±56 ml/min approximately 5 h after the start of the infusion of IGF-I, declining to 420±44 ml/min approximately 2 h after the end of the infusion. The total concentration of IGF-I (free and bound) in milk of the infused gland was significantly higher than that of the non-infused gland. The concentrations of IGF-I in carotid arterial plasma samples increased during IGF-I infusion from a mean value of 32±2 nmol/l before to a maximum of 49±3 nmol/l 5 h after the infusion commenced. Circulating concentrations of total IGF-I declined slowly after the infusion with an estimated half-life of 5 h. Infusion of saline alone did not alter mammary blood flow or the concentration of total IGF-I in milk or plasma. The results indicate that the infusion of free IGF-I into the mammary arterial supply enhances milk secretion and mammary blood flow in intact, conscious goats. The more pronounced effect in the infused compared with the non-infused gland suggests that free IGF-I acts directly on the mammary gland. The response in the non-infused gland was attenuated presumably due to association of IGF-I with plasma binding proteins during recirculation. Journal of Endocrinology (1990) 126, 437–443

1991 ◽  
Vol 131 (3) ◽  
pp. 459-466 ◽  
Author(s):  
C. G. Prosser ◽  
I. R. Fleet ◽  
A. J. Davis ◽  
R. B. Heap

ABSTRACT 125I-Labelled insulin-like growth factor-I (IGF-I) was infused as the free form directly into the pudic artery supplying one gland of lactating goats (n = 6). The infusion was for 60 min and 0·4±0·09% (s.e.m.) of the infusate was secreted into milk from the infused gland during its first passage through that gland. A large proportion of the 125I-labelled IGF-I escaped into the systematic circulation and was secreted into milk of both glands. A total of 5·2±0·4% of infused radioactivity was recovered in milk from both glands from 0 to 720 min. Radioactivity consisted of trichloroacetic acid (TCA)-precipitable and -soluble counts which were shown by gel filtration to be authentic IGF-I and degraded products of the peptide. The amount and time course of TCA-soluble radioactivity in milk from both glands was similar, suggesting degradation of 125I-labelled IGF-I at extramammary sites. Maximum specific activity for 125I-labelled IGF-I in milk from the infused gland was reached 80–120 min after the start of infusion and was 2·5-fold greater than milk from the non-infused gland. The time course of appearance of 125I-labelled IGF-I in milk suggests that transfer was via the transcellular pathway and this was further supported by comparing the pattern of transfer of [14C]sucrose and [14C]amino acids. When excess unlabelled IGF-I was included in the infusate, specific activity in milk from the infused gland was reduced to that of the non-infused gland, indicating a competitive and saturable mechanism of secretion for 125I-labelled IGF-I. Comparison of uptake and secretion of 125I-labelled IGF-I into milk from the non-infused gland with that of endogenous immunoreactive IGF-I suggests that vectorial transport of IGF-I across the mammary gland may be a significant contributor of IGF-I levels in milk. Journal of Endocrinology (1991) 131, 459–466


1993 ◽  
Vol 139 (3) ◽  
pp. 463-472 ◽  
Author(s):  
P. M. Harris ◽  
B. W. McBride ◽  
M. P. Gurnsey ◽  
B. R. Sinclair ◽  
J. Lee

ABSTRACT In vivo effects of local infusion of a variant of insulin-like growth factor-I (IGF-I), long-R3-IGF-I, into the skin were investigated using six conscious sheep with food available ad libitum. An artery and vein on the abdominal flank of each animal, as well as the saphenous artery, were catheterized so that infusion of isotopically labelled amino acids, with or without IGF-I, could be used to determine amino acid uptake by arteriovenous difference in combination with blood flow determined by dye dilution. Measurements were made on each animal prior to IGF-I infusion, at hourly intervals for the 4 h of IGF-I infusion into the skin artery, then 2 and 4 h after IGF-I infusion ceased. Numbers of cells replicating in the bulbs of wool follicles in the IGF-I-infused area and in the skin on the contralateral side of each animal were measured after labelling with 5-bromo-2′-deoxyuridine. IGF-I caused a significant increase in the skin blood flow (P<0·05), utilization of oxygen (P<0·05), uptake of cysteine (P<0·05) and phenylalanine (P<0·001), and the rate of utilization of cysteine (P<0·05) for protein synthesis. IGF-I increased amino acid uptake regardless of whether the skin was in negative or positive amino acid balance prior to infusion. During the recovery period amino acid utilization by skin returned towards preinfusion levels. No effects of IGF-I were found on replicating cell numbers in the bulbs of wool follicles. Journal of Endocrinology (1993) 139, 463–472


1991 ◽  
Vol 128 (3) ◽  
pp. 457-463 ◽  
Author(s):  
C. G. Prosser ◽  
C. Royle ◽  
I. R. Fleet ◽  
T. B. Mepham

ABSTRACT Lactating goats exhibiting widely divergent responses to short-term (4 days) treatment with bovine GH (bGH) were retrospectively divided into two groups based on the magnitude of this response. There was no difference between groups in terms of the pretreatment milk yield, but by day 4 of treatment milk secretion had increased by 4·99±2·5 (s.e.m.) ml/h (P > 0·05 compared with pretreatment) for group 1 and 22·9±2·4 ml/h (P< 0·001) for group 2. Plasma GH increased in both groups, but concentrations were significantly higher both before and during treatment in group 1 compared with group 2. Plasma concentrations of insulin-like growth factor-I (IGF-I) increased significantly during bGH treatment for both groups and there was no significant difference between the two until day 4 of treatment when levels of IGF-I in group 1 began to decline, whereas those from group 2 were maintained. Concentrations of IGF-I in milk from goats in group 1 were not significantly altered by GH administration, whereas those in goats in group 2 were increased by 40% (P < 0·01 compared with pretreatment). Levels of IGF-I in mammary secretory tissue from four animals from group 1 were not altered by bGH (2·8±0·2 and 2·77 ±0·08 nmol/kg tissue before and after treatment respectively), but were significantly (P < 0·05) increased in four animals from group 2 (2·80±0·2 and 9·9±1·1 nmol/kg tissue). Thus, it appears that the galactopoietic response in goats was associated with significantly lower levels of GH in plasma after 3 days of treatment and, more strikingly, greater amounts of IGF-I in milk and mammary tissue. This latter observation is consistent with the hypothesis that the effects of bGH on the mammary gland itself are mediated by IGF-I and that the availability of IGF-I to mammary tissue is an important component of the overall galactopoietic response to bGH. Journal of Endocrinology (1991) 128, 457–463


Endocrinology ◽  
2001 ◽  
Vol 142 (4) ◽  
pp. 1479-1488 ◽  
Author(s):  
Darryl L. Hadsell ◽  
Tatiana Alexeenko ◽  
Yann Klemintidis ◽  
Daniel Torres ◽  
Adrian V. Lee

Abstract Overexpression of des(1–3) human insulin-like growth factor I (IGF-I) in the mammary glands of transgenic mice (WAP-DES) inhibits apoptosis during natural, but not forced, mammary involution. We hypothesized that this differential response would correlate with the expression of IGF signal transducers. Forced and natural involution were analyzed in nontransgenic and WAP-DES mice beginning on day 16 postpartum. During natural involution, mammary gland wet weight was higher and apoptosis was lower in WAP-DES than in nontransgenic mice. The WAP-DES transgene had no effect on these parameters during forced involution. Mammary tissue concentrations of the transgene protein were 2- to 10-fold higher than those of endogenous IGF-I. Western blot analysis of pooled mammary tissue extracts demonstrated only slightly higher phosphorylation of the IGF signal transducers insulin receptor substrate-1 (IRS-1) and Akt in the WAP-DES than in nontransgenic mice. Dramatic early reductions in phospho-IRS-1, phospho-Akt, IRS-1, IRS-2, and Akt proteins occurred during forced, but not natural, involution. The abundance of the IGF-I receptor and the messenger RNAs for the IGF-I receptors, IRS-1 and -2, were not affected by either genotype or involution. These findings support the conclusions that mammary cells lose their responsiveness to insulin-like signals during forced involution, and that posttranscriptional or posttranslational regulation of IRS-1 and IRS-2 may play a role in this loss.


2005 ◽  
Vol 58 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Bibiana E. Dallard ◽  
Hugo H. Ortega ◽  
Juan A. Lorente ◽  
Gabriela S. Romano

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