GH Gene Research Articles

Effect of Dietary Sodium Acetate on Skin Mucus Immune Parameters and Expression of Gene Related to Growth, Immunity and Antioxidant System in Common Carp (Cyprinus carpio) Intestine

Abstract The present study investigated the possible effects of including salt of short chain fatty acid, sodium acetate (SA), on skin mucus immune parameters and immune, antioxidant and growth-related genes expression in common carp. There is little data available about the effective role of SA on immune, antioxidant and growth related genes expression as well as skin mucus immune parameters. The aim of this study was to analyse the effect of SA intake on these factors using common carp (Cyprinus carpio) as model organism. Two hundred and forty healthy common carps (mean weight = 15 ± 0.9 g) were supplied and randomly stocked into 12 fiberglass tanks 200 L (20 fish per tank) assigned to four treatments and triplicates. The study was performed in a completely randomized design. The treatments were feeding carps with experimental diets containing different levels (0.0 [control], 0.5, 1 and 2%) of SA. The skin mucus total immunoglobulin and total protein levels in fish fed 2% SA showed significant increase compared to the control group (P<0.05). Results showed a significant increase in the GH gene expression in 1 and 2% SA treatments (P<0.05). The carps fed the diet with 2% SA showed a significant increase in IGF-1 expression (P<0.05). The expression of GSTa, and GPX (antioxidant genes) revealed a significant increase in the GSTa (fish fed SA at 1% and 2% levels) and GPX gene expression with fish fed 2% SA (P<0.05). Supplementation of fish diet with SA induced a slight elevation in the intestine of all immune-related genes (TNF-α, IL-1β, IL8 and Lyz) compared to the control group (P>0.05). However, Lyz gene was significantly up-regulated in 1 or 2% SA treatments. These results confirmed beneficial effects of SA as a feed additive in common carp culture.

Association of lactation persistency with genetic variants of bovine growth hormone gene in Indian Sahiwal cows

The aim of this study was to determine the associations of persistency with genetic variants of bovine growth hormone (bGH) gene in Indian Sahiwal cows. The data pertaining to the monthly test day milk yield (MTDMY) and first lactation length (FLL) of 305 lactating Sahiwal cows over a period of 23 years (1993–2016) were subjected to analysis. Persistency of milk yield was estimated by using test day based ratio method and Wilmink b function. Mean LL was 220.06±8.15 days in all studied Sahiwal cows, however, 276.67±10.25 days in cows with ≥100 days of LL and having 500 kg MY. The peak of milk yields was achieved at third TD of the first lactation. Macrophage stimulating protein 1 (MspI) and Arthrobacter luteus1 (AluI) restriction endonucleases were used to digest the amplified regions in intron 3 and exon 5, respectively of bGHgene. The bGHMspI restriction fragment length polymorphism (RFLP) yielded TT, CT and CC genotypes, whereas bGH-AluIRFLP yielded CC, CG and GG genotypes. Significant association was found between first lactation persistency estimated using test day based ratio method and bGH-MspI polymorphism. No significant association was found between first lactation persistency and bGH-AluI polymorphism. In summary, results of present study revealed that the TT genotype of bGH–MspI gene in Sahiwal cows has better lactation persistency than other genotypes.

The 20-kDa Placental GH Variant: A New and Improved Growth Hormone?

The 20-kDa Placental GH Variant: A New and Improved Growth Hormone?

Identification of Locus GH/Alui Polymorphisms of Kuantan and Pesisir Cattle

Kuantan cattle is a local beef cattle of Riau Province that adaptive and breed well along the Kuantan river flow, found in Indragiri Hulu Regency and Kuantan Singingi Regency, have smaller morphometric performance compared to other local beef cattle and are relatively the same as Pesisir cattle. One of the genetic markers of growth determinant in beef cattle is the GH/AluI gene locus. Identification of the diversity of the GH/Alu I gene was carried out using the PCR-RFLP. Fifty four samples of Kuantan cattle consisting of 25 samples from Indragiri Hulu Regency and 29 samples from Kuantan Singingi Regency, as well as 25 samples of Pesisir cattle from BPTU-HPT Padang Mengatas Payakumbuh, West Sumatra, were used in this study. The oligonucleotida forward F-5’GCTGCTCCTGAGGGCCCTTC-3’ and reverse R-5’CATGACCCTCAGGTACGTCTCCG-3’ used in this study along 211 bp of GH Gene. The PCR mixture consisted of DNA templates 20 - 25 ng, 0.4 µL primer forward dan primer reverse (10 ng primer forward and primer reverse), 25 µL dream tag green master mix and ddH2O up to a 50 µL. PCR machine conditions consisted of 940C pradenaturation for 5 minutes, 940C denaturation for 30 seconds, annealing 650C for 1 minute, 720C extension for 50 seconds and 720C final extension for 5 minutes. Identification of GH gene diversity using AluI at an incubation temperature of 370C for 3 hours. The results in this study were found monomorphic of GH/AluI genes in Kuantan and Pesisir cattle. The monomorphic in Kuantan cattle can be used as an indicator to assess the purity of Kuantan cattle in this areas.

Association of GH polymorphisms with growth traits in buffaloes

Members of the somatotrophic axis, especially GH and IGF1, are essential for growth. The association between GH polymorphisms and growth traits was numerously studied in cattle; however, no data are available for such association studies in buffalo. Therefore, this study was conducted to screen for polymorphisms in the GH gene and to study their putative association with growth traits in 200 Egyptian buffaloes. Polymerase chain reaction single-strand conformation polymorphism and sequencing were applied to look for polymorphisms in 3 loci spanning all exons and introns of buffalo GH. The C (MspI+) >T (MspI-) SNP in intron3, which is well known in cattle, was not detected in the examined buffaloes. However, 2 missense mutations were detected in exon5: one previously detected p.Leu153Val SNP, with very low frequencies for the mutant (Val) allele and one novel p.Asn174His SNP. At weaning age, the p.Leu153Val SNP was significantly associated with weaning body weight and gain with the positive effect of the wild allele (Leu) and higher GH serum, mRNA, and protein levels in animals with Leu/Asn and Leu/His haplotypes. At yearling age, the 2 SNPs associated with yearling weight and gain with positive effect for the mutant (Val and His) alleles with increased GH, and IGF1 serum, mRNA, and protein and GHR mRNA and protein levels in animals with Val/Asn haplotype. Therefore, the selection of Egyptian buffaloes with the Val/Asn haplotype could improve the growth traits of Egyptian buffaloes at yearling age which is the target age for perfect growing.

Genetic Markers (FASN, SCD and GH gene) and Metabolic Pathways Associated with Meat Fatty Acid Profile in Cattle (Bos taurus)

Genetic Markers (FASN, SCD and GH gene) and Metabolic Pathways Associated with Meat Fatty Acid Profile in Cattle (Bos taurus)

Polymorphism of PIT‐1, PRL and GH genes in dairy cattle of the Caucasian Brown breed bred in various natural ecological zones of the Republic of Dagestan, Russia

Aim . The widespread use of so ‐ called commercial breeds leads to the loss of a unique gene pool of native breeds and the narrowing of the genetic base that is necessary to preserve and to increase the genetic diversity of cattle breeds which are still preserved. These breeds include the Caucasian Brown. In connection , the aim of this research was to study the polymorphism of PIT‐1, PRL and GH genes in dairy cattle bred in different ecological climatic zones of the Republic of Dagestan to identify the genotypes of carriers of selection ‐ significant marker alleles for their preservation and further use in the selection process. Material and Methods . Genotyping of the Caucasian brown breed cows bred in different natural climatic zones was carried out using PCR ‐ RFLP methods. The polymorphism of PIT ‐1, PRL and GH genes was studied, population analysis of their distribution in the cattle stock studied was carried out and the features of the genetic structure in the researched populations were studied in relation to the conditions of their habitat. Results . The specific allelic PIT‐1, PRL, and GH gene spectrum, characteristic for each animal population studied has been established. Homozygous and heterozygous carrier genotypes of the desired marker alleles with frequency of occurrence depending on both the gene and the animal population were identified. The genetic structural features of the genes studied in the researched populations were revealed. Conclusion . The data obtained indicate the genetic uniqueness of the Caucasian Brown breed bred in different natural climatic zones in the Republic of Dagestan and are probably associated with the manifestation of adaptations, the nature of which has developed under the influence of the prevailing ecological, natural climatic conditions of its habitat.

Effect of dietary sodium acetate on skin mucus immune parameters and expression of gene related to growth, immunity and antioxidant system in common carp (Cyprinus carpio) intestine

Abstract The present study investigated the possible effects of including salt of short chain fatty acid, sodium acetate (SA), on skin mucus immune parameters and immune, antioxidant and growth-related genes expression in common carp. There is a little data available about the effective role of SA on immune, antioxidant and growth related genes expression as well as skin mucus immune parameters. The aim of this study was to analysis the effect of SA intake on these factors using common carp (Cyprinus carpio) as model organism. Two hundred and forty healthy common carp (mean weight = 15 ± 0.9 g) supplied and randomly stocked into 12 fiberglass tanks 200 L (20 fish per tank) assigned to four treatments and triplicates. The study was performed in a completely randomized design. The treatments were feeding carps with experimental diets containing different levels (0.0 [control], 0.5, 1 and 2%) of SA. The skin mucus total immunoglobulin and total protein levels in fish fed 2% SA showed significant increase compared to the control group (P < 0.05). Results showed a significant increase in the GH gene expression in 1 and 2% SA treatments (P < 0.05). The carps were fed with diet content 2% SA showed significantly increase in IGF-1 expression (P < 0.05). The expression of GSTa, and GPX (antioxidant genes) revealed a significant increase in the GSTa (fish fed SA at 1% and 2% levels) and GPX gene expression with fish fed 2% SA (P < 0.05). Supplementation of fish diet with SA induce slight elevation in the intestine of all immune-related genes (TNF-α, IL-1β, IL8 and Lyz) compared to the control group (P > 0.05). However, Lyz gene significantly up-regulated in 1 or 2% SA treatments. These results confirmed beneficial effects of SA as a feed additive in common carp culture.

Energy evaluation of cows using genetic markers

The aim of the study was to research the polymorphism of allelic variants of somatotropin GH genes and pituitary-specific transcription factor PIT-1 and its influence on bioenergetic parameters of high-yielding of Holstein breed cows in intensive milk production technology (cold method of growing heifers, early insemination of heifers. high daily operating loads on the body, etc.). Genotypes of cows were determined by PCR. Blood DNA was examined in a genetic laboratory. Isolation of genomic DNA was performed using resin “Chelex-100”. The reaction was performed in an amplifier “Tertsyk”. For the energy assessment of first-born cows used indicators of net maintenance energy (MJ per day), net milk energy (MJ per day), total net energy consumption (MJ per day), the value of the energy index (the share of energy released from milk, %), productivity index (kilogram of 4 % milk per 1 MJ), net energy consumption per 1 MJ of milk (MJ), energy released with milk per 1 kg of metabolic mass (MJ). The best energy parameters in cows by GH gene – LL genotype, by pituitary-specific transcription factor PIT-1 – AB genotype, and among paired genotypes – LL/AB and LL/BB. In these animals, bioenergetic indicators for the first and second periods of lactation were higher than their peers of LV, BB and LV/BB genotypes by 2.0–15.2 %, with a reliable result for most traits. In particular, during the first lactation period, the advantage of cows of the LL/AB genotype over the LV/BB genotype in terms of bioenergetic indicators was 3.9–15.2 %, significantly less than in the second lactation period in the range of 1.8–7.4 %. In the genome of pituitary-specific transcription factor PIT-1, better bioenergetic parameters were found in cows of genotype AB than in cows of genotype BB. The difference in bioenergetic parameters is explained by the higher lactotropic function of the L and A alleles, and is the result of a greater complementary effect on the functioning of the alleles of the associated genes in the complex genotype. This was confirmed by the analysis of variance of one-factor complexes, which revealed a stronger influence of genotypes on bioenergetic parameters during the first period of lactation than the second. However, the strength of the influence of the paired genotype on the GH and PIT-1 genes was always high regardless of the lactation period and ranged from 8.9 to 20.9 % (P < 0.01–0.001). In the future, it is of interest to study the formation of the exterior and constitution of cows of different genetic influences under the influence of polymorphisms in the GH and PIT-1 genes.

Differential distribution and potential regulatory roles of estrogen receptor 2a and 2b in the pituitary of ricefield eel Monopterus albus

Estrogens play important regulatory roles in the pituitary of vertebrates. Two forms of estrogen receptor 2 (Esr2), namely Esr2a and Esr2b, are identified in teleosts, but their differential roles remain to be fully elucidated. In the present study, expression and potential functional roles of Esr2a and Esr2b were characterized in ricefield eels. esr2a and esr2b mRNA were broadly distributed in tissues, with high levels observed in the brain, pituitary, and gonads. In order to examine the cellular localization of Esr2a and Esr2b in the pituitary, specific antisera against ricefield eel Esr2a and Esr2b were generated, respectively. Interestingly, immunohistochemistry and Western blot analysis revealed that Esr2a and Esr2b were differentially distributed in the pituitary, with the former localized to the adenohypophysis while the latter to the neurohypophysis. Dual fluorescent immunostaining showed that immunoreactive Esr2a was present in Gh and Prl cells, but not in Lh and Fsh cells. Estradiol (E2) stimulated lhb and prl gene expression in dispersed pituitary cells of intersexual ricefield eels, but had no effects on gh, fshb, and gnrhr2 gene expression and Gh release. Results of the present study are helpful for further understanding the roles and mechanisms of estrogen signals in the pituitary.

The Effects of 20-kDa Human Placental GH in Male and Female GH-deficient Mice: An Improved Human GH?

A rare 20K isoform of GH-V (here abbreviated as GHv) was discovered in 1998. To date, only 1 research article has characterized this isoform in vivo, observing that GHv treatment in male high-fat fed rats had several GH-like activities, but unlike GH lacked diabetogenic and lactogenic activities and failed to increase IGF-1 or body length. Therefore, the current study was conducted to further characterize the in vivo activities of GHv in a separate species and in a GH-deficient model (GH-/- mice) and with both sexes represented. GHv-treated GH-/- mice had significant increases to serum IGF-1, femur length, body length, body weight, and lean body mass and reduced body fat mass similar to mice receiving GH treatment. GH treatment increased circulating insulin levels and impaired insulin sensitivity; in contrast, both measures were unchanged in GHv-treated mice. Since GHv lacks prolactin receptor (PRLR) binding activity, we tested the ability of GH and GHv to stimulate the proliferation of human cancer cell lines and found that GHv has a decreased proliferative response in cancers with high PRLR. Our findings demonstrate that GHv can stimulate insulin-like growth factor-1 and subsequent longitudinal body growth in GH-deficient mice similar to GH, but unlike GH, GHv promoted growth without inhibiting insulin action and without promoting the growth of PRLR-positive cancers in vitro. Thus, GHv may represent improvements to current GH therapies especially for individuals at risk for metabolic syndrome or PRLR-positive cancers.

Obesity and regulation of human placental lactogen production in pregnancy.

The four genes coding for placental members of the human (h) growth hormone (GH) family include two that code independently for placental lactogen (PL), also known as chorionic somatomammotrophin hormone, one that codes for placental growth hormone (PGH) and a pseudogene for which RNA but no protein product is reported. These genes are expressed preferentially in the villus syncytiotrophoblast of the placenta in pregnancy. In higher primates, the placental members, including hPL and PGH, are the result of multiple duplication events of the GH gene. This contrasts with rodents and ruminants, where PLs result from duplication of the prolactin (PRL) gene. Thus, unlike their mouse counterparts, the hPL and PGH hormones bind both lactogenic and somatogenic receptors with varying affinity. Roles influenced by nutrient availability in both metabolic control in pregnancy and maternal behaviour are supported. However, the effect maternal obesity has on the activation of placental members of the hGH gene family, particularly the expression and function of those genes, is poorly understood. Evidence from partially humanised hGH/PL transgenic mice indicates that both the remote upstream hPL locus control region (LCR) and more gene-related regulatory regions are required for placental expression in vivo. Furthermore, a specific pattern of interactions between the LCR and hPL gene promoter regions is detected in term placenta chromatin from women with a normal body mass index (BMI) in the range 18.5-25kgm-2 by chromosome conformation capture assay. This pattern is disrupted with maternal obesity (class II BMI>35kgm-2 ) and associated with a >40% decrease in term hPL RNA levels, as well as serum hPL but not PRL levels, during pregnancy. The relative importance of the chromosomal architecture and predicted properties for transcription factor participation in terms of hPL production and response to obesity are considered, based on comparison with components required for efficient human pituitary GH gene expression.

Analysis of polymorphism of CAPN1 and GH genes in cattle of Kazakh White-Headed breed in association with the peculiarities of beef productivity

The intensive development of genetics at the molecular level has now opened up the possibility for breeders to identify and study genes that are directly or indirectly related to desirable economically useful traits. The purpose of the research was to identify desirable genotypes in the breeding of Kazakh White-Headed cattle based on the genes-markers of meat productivity of calpain (CAPN1) and somatotropin (GH) for use in breeding to increase meat productivity and beef quality. Experimental researches have been carried out on steers of the Kazakh White-Headed breed on the basis of the APC collective farm “Gigant” in the Blagodarnensky district in the Stavropol Territory. Analysis of growth and development indicators of calves has shown that the value of live weight and average daily gains was higher in calves carrying the C allele at calpain gene locus and V allele at somatotropin gene locus. Dominant alleles C and V in the homozygous state characterize the desired genotype of calves. During weaning the studied indicators were higher with a diff erence on average up to 13,0 % in young animals of homozygous genotypes (CC and VV). The largest number of muscle fi bers has been observed in steers with the desired CC and VV genotypes. They outperformed their herdmates with GG genotype by 36,82 pcs/мм² or 19,7 % in calpain gene group (CAPN1) by 55,7 pcs/мм² or 31,4 % in somatotropin gene group (GH), respectively. The diameter of muscle fibers in carcasses with the desired genotype was less by 4,23 microns or 11,9 %, and by 6,82 microns or 16,8 %. The meat of steers with homozygous CC and VV alleles according to the studied genes differed from the meat of animals with GG and LL genotypes by 12,6 % in calpain gene (CAPN1) and 15,1 % in somatotropin gene (GH). The connective tissue content was higher in animals with the undesirable type of G and L alleles than in animals of the desired genotype, by 2,13 and 3,34 abs. percent’s. The area of the eye of loin in animals of desired VV genotype of somatotropin cluster (GH) was higher than in animals of CC genotype of calpain cluster (CAPN1) by 4,84 cм² or 10,1 %.

A combination of rapeseed, cottonseed and peanut meal as a substitute of soybean meal in diets of Yellow River carp Cyprinus carpio var

A feeding trial was conducted to evaluate the results of replacing soybean meal (SBM) with other blend plant protein (BP) (rapeseed meal, cottonseed meal and peanut meal) sources on growth, fish body composition, biochemical parameters, non-specific immune index and gene expression of growth hormone/insulin-like growth factor-1 in Yellow River carp Cyprinus carpio. The results showed that the 600 g/kg replacement with BP in diet did not affect the growth performance of Yellow River carp, but the 800 g/kg SBM replacement diet could depress the growth of fish (p < .05). The 800 g/kg SBM replacement diet significantly impacted the superoxide dismutase, malondialdehyde contents, lysozyme, alanine aminotransferase and aspartate aminotransferase activities (p < .05). Fish fed 800 g/kg SBM replacement diet showed lowest insulin-like growth factor 1 and highest growth hormone level than that of other diets (p < .05). Both gene expression levels of GH and IGF-I in hepatic showed significant difference among dietary treatments (p < .05), and the lowest GH and IGF-I mRNA level in liver were found in fish fed 800 g/kg SBM replacement diet (p < .05). In conclusion, no more than 600 g/kg SBM could be replaced by BP in diet of Yellow River carp without adverse effects on the growth performance. However, 800 g/kg SBM replacement with BP in diet inhibited the growth performance, affected some blood parameters and immune response index, and down-regulated GH and IGF-1 gene expression of liver in Yellow River carp. Further, GH level in serum was negatively correlated with GH mRNA level in liver; meanwhile, serum concentrations of IGF-I were positively correlated with hepatic IGF-I mRNA expressions.

Evolution of placentation in cattle and antelopes.

Bovids have enjoyed great evolutionary success as evidenced by the large number of extant species. Several important domestic animals are from this family. They derive from both subfamilies: cattle and their kin belong to Bovinae and sheep and goats to Antilopinae. The premise of this review, therefore, is that evolution of reproduction and placentation is best understood in a context that includes antelope-like bovines and antelopes. Many key features of placentation, including hormone secretion, had evolved before bovids emerged as a distinct group. Variation nevertheless occurs. Most striking is the difference in fusion of the binucleate trophoblast cell with uterine epithelium that yields a transient trinucleate cell in bovines and many antelopes, but a more persistent syncytium in wildebeest, sheep and goat. There is considerable variation in placentome number and villus branching within the placentome. Many antelopes have right-sided implantation in a bicornuate uterus whilst others have a uterus duplex. Finally, there has been continued evolution of placental hormones with tandem duplication of PAG genes in cattle, differences in glycosylation of placental lactogen and the emergence of placental growth hormone in sheep and goats. The selection pressures driving this evolution are unknown though maternal-fetal competition for nutrients is an attractive hypothesis.

MON-LB014 Autosomal Dominant Growth Hormone Deficiency Due to a Novel c.178g&amp;gt;A Mutation in the GH1 Gene Is Caused by Alternative Splicing to Produce a Small GH Isoform

Introduction: Growth hormone (GH) plays a vital role in human physiology. Mutations in GH1 cause isolated growth hormone deficiency (GHD). The most frequent cause of familial growth hormone deficiency is Type II autosomal dominant GHD (isolated GHD type II) due to several heterozygous GH1 mutations. These mutations have been shown to (a) produce shorter isoforms of GH that do not bind to growth hormone receptors, (b) cause diminished secretion of GH, or (c) result in misfolded GH protein. Methods: Genomic DNA from patients with familial GHD was enriched for the coding exons using hybrid capture technology, and GH1 was sequenced using Next Generation Sequencing technology. The p.A34T mutant protein was expressed in bacteria, and binding to GHR was studied by surface plasmon resonance technology. Computational prediction of transcription indicated that alternative splicing is likely to produce a shorter GH variant with skipping of exon 3 in GH1. Mammalian cell-based studies incorporating transfection of whole GH1 gene containing exons/introns were used to study transcriptional effects. RNA was isolated from cells transfected with WT and mutant GH1 gene and analyzed by RT PCR using primers in the second and fifth exons of GH1 that could identify all possible isoforms of GH1 mRNA. Results: GHD was identified in three female siblings aged 3.25-6.33 years (Ht SDS -3.21 to -1.13, peak GH 2.9-6.6 ng/mL); their mother had previously been diagnosed with GHD at age 12.33 years (Ht SDS -3.44, GH peak < 2 ng/mL). Sequencing of GH1 identified a novel heterozygous variant (c.178G>A; p.Ala34Thr) not found in the Broad ExAc dataset representing >60,000 children without the severe childhood-onset disease. Functional studies using whole gene transfection showed that the c.178G>A mutation leads to alternate splicing resulting in increased production of the shorter 17.5kD isoform of GH due to exon 3 skipping. Results were confirmed by quantitative RT-PCR as well as GH secretion assays, which showed a lower level of GH production from cells transfected with the GH1 gene containing the c.178G>A mutation. The SPR based receptor binding assay and cell proliferation assay using bacterially expressed proteins showed that once produced, the GH protein with the A34T mutation behaves similar to WT GH protein. All these results confirm that the cause of GHD due to the c.178G>A mutation in GH1 is due to altered transcription leading to the production of the shorter 17.5 kD isoform of GH protein and not due to the amino acid change A34T that is caused by the mutation. Conclusion: The presence of a heterozygous GH1 variant (c.178G>A, p.Ala34Thr) in four individuals with GHD suggests that this is a novel cause of IGHD type II. Production of the smaller 17.5 kD GH isoform results in reduced overall GH secretion and loss of binding to GHR due to competition with the normal GH protein, explaining the dominant-negative phenotype.

SAT-267 Pregnancy in Acromegaly: Report of Five Cases

Introduction: In acromegaly, there are changes in growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin, hormones very important in pregnancy as well. Despite novel treatments, pregnancy in acromegaly is uncommon, remaining a challenge for clinicians.We report seven pregnancies in five women with acromegaly. Clinical Cases: Five acromegalic patients (17 – 35 years-old) underwent seven pregnancies. All patients had macroadenoma: four were submitted to non-curative neurosurgery and two of them had gamma-knife radiosurgery. One patient had medical treatment prior to curative transsphenoidal surgery (TSS).One patient being treated with estroprogestative for hypogonadism had a spontaneous pregnancy; three others had pregnancy just before biochemical diagnosis of acromegaly, one of them had also a spontaneous abortion and another successful pregnancy during treatment with somatostatin receptor ligand (SRL); the last patient become pregnant during treatment with SRL, prior to TSS.Monitoring was made with IGF-1, GH (assay with no distinction of pituitary GH versus placental GH), prolactin (PRL) and visual field; pituitary imaging was performed after pregnancies in all.All women conceived naturally, two being on treatment with SRL (discontinued after confirmation of pregnancy). No treatment for acromegaly was administered before delivery. All patients had physiologic pregnancies, delivered full-term healthy babies, no malformations or metabolic disruptions; one did not breast-feed; another one had a spontaneous abortion 2 days after confirmation of pregnancy.No patient developed either hypertension, pre-eclampsia or gestational diabetes.In three cases, the clinical suspicion of acromegaly had risen during pregnancy and the diagnosis was made 1 year after delivery. The one with three pregnancies had controlled secretion of GH on Lanreotide and GH and IGF-1 levels remained stable during pregnancy.The woman with gonadotroph deficiency after TSS and GK and substitutive therapy had a decrease in IGF-1 during pregnancy (45 %), which after delivery returned pathologically to before pregnancy values; GH levels remained stable.The last patient, who became pregnant with uncontrolled acromegaly on Pasireotide, had increased, but stable GH and IGF-1 (2 X upper limit of normal) before, during and after pregnancy. TSS performed 3 years after delivery cured the disease. Conclusion: From our experience, patients with acromegaly may have normal babies, even in patients with uncontrolled hypersecretion and lack of medical treatment during pregnancy. The consensus is, however, that there is no indication to use medication to control GH hypersecretion or tumor size in acromegaly patients during pregnancy (1). Reference: (1) Muhammad A, Neggers SJ, van der Lely AJ. Pregnancy andacromegaly. Pituitary. 2017;20(1):179–184. doi:10.1007/s11102-016-0740-3

MON-283 IGF-1 Levels During Normal Pregnancy

Pregnancy is associated with a physiological GH excess, where maternal pituitary GH is suppressed by effect of placental GH on the hepatic receptor, increasing IGF-1 serum levels1. However, it is also described that estrogens and progesterone are responsible for reduction in IGF-1 by direct hepatic action through the inhibition of the JAK-STAT pathway that results in GH resistance, being more clear at the beginning of pregnancy.2 Acromegaly is a rare disorder in which GH axis is deregulated and IGF-1 is the most reliable biochemical marker for diagnosis and monitoring. It is know that secondary hypogonadism associated with these pathology decreases fertility rates. Nonetheless, improvement of acromegaly treatment and greater access to assisted reproductive technology increase pregnancy rates in this population. The follow-up of pregnant acromegalic women acquires relevance for the comorbidities of this association and depends on the adequate interpretation of the IGF-1 values. Then, due to changes in concentration and action of IGF-1 during pregnancy3, it is important that each laboratory establish their specific reference values. For that reason we analyzed serum samples from 80 healthy pregnant women living in the Metropolitan Area of Buenos Aires (AMBA): 22 were in the 1st trimester (1T), 29 in the 2nd (2T) and 29 in the 3rd (3T). All women were between 30 and 40 years old, had no endocrinopathies or metabolic diseases. Serum IGF-1 was measured by Immulite 2000 Siemens, and Prism8 GraphPad was used for statistical analysis, calculating ranges for each trimester defined as 2,5 and 97,5 percentiles. Ranges obtained were: 64,5-165,0 ng/ml, 78,9-201,0 ng/ml and 96,1-344,0 ng/ml for 1T, 2T and 3T, respectively. Significant differences were observed between 3T and the other trimesters (1T and 2T). We also compared these ranges with our reference values from healthy non-pregnant women in the same age, and found that 3T has significantly higher values ​​of IGF-1 (55,8-188,4 ng/ml vs. 96,1-344,0 ng/ml respectively). In conclusion, IGF-1 levels during the first two trimesters of pregnancy remain within the normal range, and there is a significant increase during the third trimester. Given that IGF-1 plays an essential role during pregnancy, it is important to report ranges in healthy pregnant women to contribute in the follow-up of patients with acromegaly who get pregnant. Although our results are in agree with the available literature, it is necessary to increase the number of healthy pregnant women to establish reference values of IGF-1. 1Frankenne et al (1988). The physiology of growth hormones in pregnant women and partial characterization of the placental GH variant. Journal of Clinical Endocrinology and Metabolism 66:1171-1180 2Leung et al (2004). Estrogen regulation of growth hormone action. Endocrine Reviews 25:693-72 3Muhammad et al (2017). Pregnancy and acromegaly. Pituitary 20:179-184

SUN-LB51 Growth Hormone Deficiency and Resistance Result in Altered Intestinal Gross Anatomy and Morphology in Mice at Adult and Older Adult Timepoints

Growth hormone (GH) plays an important role in sustaining intestinal integrity. That is, GH has been shown to decrease intestinal permeability and bacterial translocation and alter gut functions like macronutrient absorption and immune function. To date, however, few studies have investigated how GH action – especially global knockdown of GH action - alters intestinal gross anatomy and morphology. This study characterized the intestinal gross anatomy and morphology of two mouse lines with decreased GH action (with improved health-span and insulin sensitivity): 1) GH gene disrupted (GH-/-) mice (GH deficiency) and 2) GH receptor knockout (GHR-/-) mice (GH resistance). Intestines from GH-/- and GHR-/- mice and their respective littermate controls at adult (12-13 mo.) and older adult (19 mo. and 24 mo., respectively) were used for this study. Both length and weight of small and large intestines were measured at the time of dissection. Six sections for the small intestine and four sections for the large intestine were prepared using a swill roll technique. Images were taken at 100x magnification with a Nikon Eclipse E600 microscope, and villus height, crypt depth, and muscle thickness were measured using ImageJ. All measurements were analyzed using Student t-test, and Cohen’s d effect size was used to compare the intestinal phenotype between lines. Both GHR-/- and GH-/- displayed altered intestinal gross anatomy and morphology. GHR-/- mice at 13 mo. of age had significantly shorter small and large intestines compared to controls. Morphologically, GHR-/- mice also showed significantly decreased villus height in the duodenum and decreased villus height and crypt depth in the jejunum. Likewise, GHR-/- mice at 24 mo. of age had significantly decreased intestinal length, and circumference in both small and large intestines with significantly decreased crypt depth in the ileum. Similar to GHR-/- mice, GH-/- mice at both 12 mo. and 19 mo. of age exhibited significantly shorter small and large intestines compared to controls with significantly smaller circumferences. Duodenum and jejunum of GH-/- mice also had a significant decrease in villus height in the duodenum and jejunum. In this study, decreased GH action is apparent in significantly affecting intestinal morphology and gross anatomy. GHR-/- and GH-/- mice had similar changes in gross anatomy (i.e. length and circumference) and villus height of the duodenum and jejunum. Similar changes to intestinal gross anatomy and morphology were also seen across the different ages in the mice. These findings suggest that decreased GH action influences the gross anatomy of both small and large intestines, and yet has a distinctive section-dependent impact on intestinal morphology. Research needs to be conducted to understand how these structural changes relate to gut function and assess intestinal phenotype at a younger ages in these mouse lines.

The Linkage of Polymorphic Variants of Genes Gh, Prl, and Pit-1 and Milk Productivity of Cows with Morphology of Cumulus-Oocyte Complex Sampled Post Mortem

In recent years, the aim of dairy cattle breeding was to increase milk productivity traits. However, there is an observed decrease of fertility traits of cows, and, as a result, early culling of animals. This is due to the fact that causes of decreased reproduction are sometimes impossible to determine and its signs are difficult to estimate. One of the causes for decreasing fertility of cows is the decline in the quality of oocytes capable of fertilization. Therefore, a study into the ratio between the number and quality of oocytes capable of fertilization and the level of milk productivity in cows, as well as association with polymorphic variants of the GH, PRL, and Pit-1 genes, is of scientific interest. The aim of this study was to determine the dependence of the quality and quantity of cow COC obtained post mortem on the level of milk productivity and genetic profile for the genes GH, PRL, and Pit-1. There was high frequency of allele L of the GH gene, 0.942; allele A of the PRL gene, 0.889; and allele B of the Pit-1 gene, 0.710. High average content of COC per ovary was obtained in a group of animals with LL genotype of the GH gene (LL to LV +7.54 units, p ≤ 0.05), and a significant portion of them were viable (LL to LV +4.5 units, p ≤ 0.05). In individuals with the AA genotype of the PRL gene, the average number of isolated viable COC per ovary was higher than in those with the AB genotype (+4.84 units, p ≤ 0.05). Analysis of the association of polymorphic variants of the Pit-1 gene with the quantity and quality of COC did not reveal significant differences in the studied group of individuals. Assessment for the relationship of polymorphic variants of the studied genes with the breeding value (BV) indices of milk productivity, milk fat, and protein content showed that only animals with the LV genotype exceeded their peers with the LL genotype of the GH gene in milk fat and protein content by 8.3 kg (p ≤ 0.05) and 6.0 kg (p ≤ 0.01), respectively. Average calculated breeding value based on quantity of COC of individuals in the studied groups revealed no significant difference.