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J M Suttie

Publications and source records attributed to J M Suttie.

At least 19 recordsLinked to original sources

Effects of testosterone on pedicle formation and its transformation to antler in castrated male, freemartin and normal female red deer (Cervus elaphus).

Pedicles and antlers are male deer secondary sexual characters. As such, development of these structures is under the control of androgen hormones. Pedicle growth is caused by increasing and elevated plasma testosterone (T) levels, whereas first antler transformation from a fully formed pedicle occurs when the T levels are decreasing. Castration prior to pedicle initiation abrogates future pedicle and antler formation. Female deer also have the potential to develop pedicles and antlers, but they do not normally express this phenotype due to lack of sufficient androgen stimulation. Previous studies have shown that female white-tailed deer could be readily induced to grow pedicles as well as antlers by singular administration of exogenous androgens (EA), but in red deer (Cervus elaphus) singular or irregular EA treatment could only stimulate castrated male, normal or ovariectomised females to grow pedicles, but not antlers. The present study was set out to test whether these EA-induced pedicles in red deer failed to give rise to antlers was because they were constitutively incapable of doing so, or because the plasma T profile naturally exhibited in intact stags was not achieved by the androgen treatment used in these previous studies. Eight castrated red deer stag calves, 3 freemartins (females which were born co-twin to males), and 3 normal female red deer were used in the present study and treated with EA, either as biweekly injections for the castrates or as implants for freemartin and females until the late stage of pedicle growth. Blood sampling was carried out biweekly for the analyses of plasma T and IGF1 concentration. The results showed that the natural plasma T profile in the experimental deer was successfully mimicked through regular EA treatment and subsequent withdrawal at late pedicle growth stage. All castrated males, 2 out of 3 freemartin, and 1 out of 3 normal female red deer formed not only pedicles, but also antlers. Based on these results, we conclude that EA-induced pedicles at least in red deer of the genus Cervus, like those in the genus Odocoileus, are constitutively capable of giving rise to antlers, if they are of sufficient height.

Animals↗

Tissue collection methods for antler research.

The rapid growth of deer antlers makes them potentially excellent models for studying tissue regeneration. In order to facilitate this, we have developed and refined antler tissue sampling methods through years of antler research. In the study, antler tissues were divided into three main groups: antler stem tissue, antler blastema and antler growth centre. For sampling stem tissue, entire initial antlerogenic periosteum (around 22 mm in diameter) could be readily peeled off from the underlying bone using a pair of rat-toothed forceps after delineating the boundary. Apical and peripheral periosteum/ perichondrium of pedicle and antler could only be peeled off intact when they were cut into 4 quadrants and 0.5 cm-wide strips respectively. Antler blastema included blastema per se, and potentiated and dormant periostea. Blastema per se was sampled after it was divided into 4 quadrants using a disposable microtome blade. Potentiated and dormant periostea were collected following the same method used for sampling peripheral periosteum of pedicle and antler. The antler growth centre was divided with a scalpel into 5 layers according to distinctive morphological markers. The apical skin layer could be further separated into dermis and epidermis using enzyme digestion for the study of tissue interaction. We believe that the application of modern techniques coupled with the tissue collection methods reported here will greatly facilitate the establishment of these valuable models.

Animals↗

Tissue interactions and antlerogenesis: new findings revealed by a xenograft approach.

Tissue interactions play a pivotal role in organogenesis. Here we describe a xenograft approach to investigate how heterotypic tissue interactions control antler formation in deer. Deciduous antlers grow from the apices of permanent protuberances, called pedicles. Histogenesis of pedicles depends on the antlerogenic periosteum (AP). Pedicles and growing antlers are made up of interior osseocartilage (a mixture of bone and cartilaginous tissue) and exterior skin. In a previous study we hypothesised that pedicle growth may result from mechanical interactions between the interior and exterior components whereas antler generation from a pedicle would involve molecules communicating between the interior and exterior components. To test this hypothesis, we subcutaneously transplanted AP of red deer (Cervus elaphus), either alone or with future pedicle skin, onto nude mice. The results showed that under the nude mouse skin, subcutaneously xenografted AP alone not only could form pedicle-shaped protuberances but also could differentiate into well-organised pedicle-like structures. The overlying mouse skin accommodated the expansion of the grafted AP by initial mechanical stretching and subsequent formation of new skin. Nude mouse skin was not capable of participating in antler tissue formation. However, grafted deer skin together with AP may have successfully rescued this failure after wounding, which highlights the necessity of the specificity of the overlying skin for antler tissue generation. Therefore, we conclude that it is the interaction between the antlerogenic tissue and the overlying skin that results in antlerogenesis: reciprocal mechanical interactions cause pedicle formation, whereas reciprocal instructive interactions induce first antler generation.

Animals↗

No direct mitogenic effect of sex hormones on antlerogenic cells detected in vitro.

Deer pedicles, antecedents of antlers, develop from a specialized periosteum (antlerogenic periosteum) which overlies the lateral crest of the deer frontal bone. The initiation of pedicle growth is triggered by androgen hormones. Thus far, it is not known whether pedicle initiation is caused by direct stimulation of androgen hormones on the antlerogenic periosteum or whether some intermediate mechanisms are necessary. The present study took an in vitro approach to investigate whether sex hormones have direct mitogenic effects on primary cultured antlerogenic periosteal cells (antlerogenic cells). Antlerogenic cells were obtained from two 5-month-old red deer calves. The cells were passaged twice and then treated with testosterone, dihydrotestosterone, and estradiol. The proliferation assays showed that no direct mitogenic effects on the second passage antlerogenic cells could be detected with any of the sex hormone treatments (P > 0.05). Testosterone-binding studies showed that at the second passage, specific testosterone-binding sites were present in the antlerogenic cells. Therefore, we conclude that androgens do not have mitogenic effects on antlerogenic cells in vitro. Our results suggest that pedicle formation may not be the result of direct stimulation of androgen hormones on antlerogenic tissue. Instead, androgen hormones may only allow the process to proceed by increasing the sensitivity of antlerogenic cells to mitogens, e.g., some growth factors.

Animals↗

Deer antlerogenic periosteum: a piece of postnatally retained embryonic tissue?

This article reviews the research findings on the piece of periosteum overlying the lateral crest of prepubertal deer frontal bone, known as antlerogenic periosteum (AP). AP was initially discovered by Hartwig and Schrudde in 1974 when searching for the tissue that gives rise to antlers. In their experiment, when AP was transplanted elsewhere on the deer body it formed ectopic antlers. This clearly shows that AP possesses full self-differentiating ability, an attribute that can only be paralleled by embryonic tissue in mammals, like lateral plate mesoderm (LPM). Studies along this line by Goss in the 1980s further demonstrated that AP also holds the patterning information for antler formation. In the 1990s, our group carried out a series of studies on this unique tissue. The results showed that some of the critical features of AP resemble those of embryonic tissues, such as the astonishing growth potential in vivo and in vitro, and rich glycogen content. Histological observations and cell lineage tracing using a genetic marker convincingly demonstrate that pedicles and antlers are the derivatives of AP. Based on these findings, we advanced a hypothesis that AP is a piece of postnatally retained embryonic tissue. Morphological and histological examinations on the presumptive antler growth regions in deer prenatal life showed that the growth of primordial pedicles is initiated in the early pregnant stage (about 55 days) but then ceases (about 100 days) and is subsequently repressed at the late stage of pregnancy. The epidermis overlying the primordial pedicles resembles the apical ectoderm ridge (multicellular layer). These results strongly support our hypothesis. The results from the specific comparison between deer antler formation (from AP in postnatal) and mammalian limb development (from LPM in prenatal) showed that the ontogeny of antlers and limbs are comparable, and that deer antler has the same level of regulative properties as mammalian limbs. We believe that revealing the mechanism underlying the retention of embryonic tissue properties by AP until deer postnatal life will have important implications in biomedical research. Antler formation from AP offers an ideal model to work with in investigating how a self-differentiating system functions.

Animals↗

Effects of testosterone either alone or with IGF-I on growth of cells derived from the proliferation zone of regenerating antlers in vitro.

Deer antlers are male secondary sexual characters and are the fastest growing mammalian tissue. As such, both androgens and growth factors play a major role in antler development. The timing of the antler cycle is controlled by the seasonal fluctuations of testosterone, and the actual growth of antlers is mainly stimulated by growth factors including insulin-like growth factor-1 (IGF-I). However, whether or not testosterone at low levels plays a growth-promoting role during antler formation is controversial. In the present study, we took an in vitro approach to investigate whether testosterone either alone or with IGF-I had mitogenic effects on mesenchymal or cartilaginous cells derived from the proliferation zone of regenerating antlers. In addition, a binding assay was carried out to determine whether the specific binding sites for testosterone were preserved after cell disaggregation. The results showed that testosterone either in physiological concentrations or at low levels did not exert direct mitogenic effects on antler cells derived from the proliferation zone in serum-free medium in vitro (P>0.05), even if the specific binding sites for testosterone in these cells were well preserved. Likewise, testosterone in a very wide range of concentrations not only failed to enhance (P>0.05), but at certain levels (0.1-5 nM) impaired the mitogenic effects of IGF-I on these antler cells in vitro (P<0.001). Therefore, these results support neither a conclusion that low level testosterone has growth-promoting effects on antler formation nor the hypothesis that testosterone effects may be achieved through sensitizing these antler cells to the mitogenic effects of IGF-I.

Animals↗

Histological studies of pedicle skin formation and its transformation to antler velvet in red deer (Cervus elaphus).

Deer antlers and their antecedent pedicles are made up of two components, interior osseocartilage and exterior integument. In a previous study, we described that histogenesis of the interior osseocartilage proceeds through four ossification stages. These are intramembranous (IMO), transition (OPC), pedicle endochondral (pECO), and antler endochondral (aECO). In the present study, we used histological techniques to examine pedicle skin formation and its transformation to antler velvet. The results showed that pedicle skin initiated from the apex of a frontal lateral crest and was formed through three distinctive stages. These stages are 1) compression of the subcutaneous loose connective tissue at the OPC stage, 2) stretching of the undulated epidermis at the early pECO stage, and 3) neogenesis of the skin and its associated appendages at the mid pECO stage. Transformation into antler velvet, which occurs at the late pECO stage, is mainly associated with alteration in the skin appendages. This alteration includes the loss of arrector pili muscle and sweat glands, and the gain of the large bi- or multi-lobed sebaceous glands. These results suggest that pedicle skin expansion occurs to release the mechanical tension created by underlying forming antlerogenic tissue, initially in response to it by mechanical stretch, and then by neogenesis of skin. In turn, the stretched pedicle skin may exert mechanical pressure on the underlying antlerogenic tissue causing it to change in ossification type. Antler velvet generation may be accomplished by both mechanical stimulation and chemical induction from the underlying pECO stage antlerogenic tissue. If this hypothesis is correct it is likely that mechanical stimulation would drive skin formation and chemical induction then determine skin type. Furthermore, asynchronous transformation of the interior and exterior components during pedicle formation and antler generation may result from the delayed chemical induction and the way antler velvet initially generates. The results from both mitotic cell labelling of the basal layer and ultrastructure of the basement membrane of the apical skin in the study support these hypotheses.

Aging↗

Toxicological evaluation of New Zealand deer velvet powder. Part I: acute and subchronic oral toxicity studies in rats.

Potential toxic effects of acute and subchronic dosage regimens of deer velvet powder have been assessed in rats following OECD guidelines. In the acute study, rats of both sexes were exposed to a single dose of 2 g/kg body weight. There was no mortality or other signs of toxicity during 14 days' observation. Furthermore, no significant alteration either in relative organ weights or their histology was discernible at terminal autopsy. In the 90-day subchronic study, deer velvet was administered in 1 g/kg daily doses by gavage to rats. A control group of rats received water only. There was no effect on body weight, food consumption, clinical signs, haematology and most parameters of blood chemistry including carbohydrate metabolism, liver and kidney function. No significant differences were seen between the mean organ weights of the adrenal, kidney and brain in rats treated with deer velvet and control rats. However, there was a significant difference (P<0.05) in the group mean relative liver weight (3.52 +/- 0.30 vs 3.81 +/- 0.26 g/100 g body weight) of deer velvet-treated and control male rats. The gross necropsy and pathological examination of rats treated with deer velvet did not reveal any abnormalities in tissue morphology. Based on these results, it may be concluded that rats had no deer velvet treatment-related toxicological and histopathological abnormalities at the doses administered, despite the observed minor changes in liver weight.

Administration, Oral↗

Differences in pituitary cell number but not cell type between genetically lean and fat Coopworth sheep.

Coopworth sheep selected for low backfat (lean genotype) have been shown to have heavier pituitary glands than those selected for high backfat (fat genotype). This paper investigated whether this difference was due to an increase in pituitary cell number or cell size and whether the relative proportions of different pituitary cell types differed between the genotypes. In three separate trials, ram lambs aged 6 to 8 months were slaughtered and the pituitary glands were processed for stereological or immunocytochemical studies. The pituitary glands of lean genotype sheep were between 30 and 60% heavier than those of the fat sheep. Lean sheep had a significantly (P<0.05) larger cross-sectional area of the pituitary fossa (96.6 vs. 81.7 mm(2)) than fat genotype sheep. The pituitaries from lean sheep contained significantly more total cells than fat sheep (Trial 1: 290 vs. 183 million cells, P<0.01; Trial 2: 353 vs. 239 million cells, P <0.05). The volume of individual cells did not differ between the genotypes. Trial 3 showed that there was no difference between lean and fat sheep in the percentage of cells staining positive for the five pituitary hormones studied. It is concluded that the larger pituitary glands of lean compared to fat genotype sheep are a result of a nonspecific increase in the size of the whole gland through increased cell numbers, with no change in cell size or the relative proportion of different cell types.

Animals↗

Effects of insulin-like growth factor 1 and testosterone on the proliferation of antlerogenic cells in vitro.

Androgen hormones and growth factors are implicated in pedicle formation and antler transformation in deer. The potential to form a pedicle and an antler is only found in the antlerogenic periosteum (AP) overlying the presumptive antler growth region. Histological studies (Li and Suttie, '94) showed that AP consists of an inner cellular layer and an outer fibrous layer. Pedicle and antler are mainly derived from the cellular layer cells of the AP. Ossification takes place in four stages: intramembranous (IMO), transitional (OPC), pedicle endochondral (pECO) and antler endochondral (aECO). However, the precise mechanism whereby androgen hormones and growth factors control pedicle and antler formation is unknown. The aim of this study was to use cell culture techniques to investigate how testosterone and IGF1 affects the proliferation of antlerogenic cells from the four ossification stages of pedicle/antler in vitro. The results showed that in serum-free medium IGF1 stimulated the proliferation of antlerogenic cells from all four ossification stages in a dose-dependent manner. In contrast, testosterone alone did not show any mitogenic effects on these antlerogenic cells. However, in the presence of IGF1, testosterone increased proliferation of the antlerogenic cells from the IMO and the OPC stages (pedicle tissue), and reduced proliferation of the antlerogenic cells from transformation point (TP) and aECO stages (antler tissue). Therefore, the results from the present in vitro study support the in vivo findings that androgen hormones stimulate pedicle formation but inhibit antler growth. The change in the mitogenic effects of testosterone on antlerogenic cells from positive to negative occurs approximately at the change in ossification type from OPC to pECO. Therefore, these results reinforce the hypothesis that the transformation from a pedicle to an antler takes place at the time when the ossification type changes from OPC to pECO rather than at the time when the pedicle grows to its full species-specific height.

Animals↗

Effects of photoperiod on the cessation of growth during autumn in male red deer and growth hormone and insulin-like growth factor-I secretion.

Male red deer undergo seasonal cycles of food intake and growth rate, which are high during spring and low during winter, despite high quality food ad libitum. Hormonal profiles during the cessation of growth in autumn and the potential role of photoperiod in the timing of the observed changes have been investigated. Whether this seasonal decrease in growth affected the response of GH and IGF-I to fasting was also examined. Two groups of six male 1-year-old red deer were exposed to different photoperiods after the summer solstice. One group (C) was given a simulated natural photoperiod while the other group (SS) was maintained on a summer solstice photoperiod (16L:8D). GH was measured in blood collected continuously and divided into pools every 5 min for 24 h in the fed state and after a 48-h fast on two occasions; the first was in November before photoperiod manipulation began and the second was in April approximately 16 weeks after initiating treatments. IGF-I, prolactin, and testosterone were measured in weekly samples. Individual live weight and group food intake were also measured each week. The normal growth pattern seen in the C group was delayed in the SS group. Thus, from 7 March until the second GH sampling on 11 April the live weight of deer in group C fell; in contrast, deer in group SS continued to grow (-43 vs 186 g/day s.e.d. = 65.5, P < 0. 01). Food intake changes reflected the pattern of growth in both groups. Mean GH (P < 0.05), GH pulse amplitude (P < 0.01), and IGF-I (P < 0.001) declined in both groups from November to April. This decline was more marked in group C and in April these parameters were all lower in group C than in group SS (GH, P < 0.05; IGF-1, P < 0.01). Prolactin levels in April were also lower in group C than in group SS (P < 0.01); testosterone was not affected by treatment. Fasting increased mean GH and GH pulse amplitude in both groups in November (P < 0.05). In April, the fasting response differed between the groups. In group C, mean GH, pulse amplitude, and pulse frequency were all greater in the fasted state than in the fed state (P < 0.05), while in group SS there were no significant differences (P > 0.05). IGF-I was lower in the fasted state than in the fed state at both sampling dates (P < 0.001). The seasonal decline in food intake and growth is associated with decreased GH, IGF-I, and prolactin concentrations, and increased testosterone and the GH response associated with fasting. All these changes except those of testosterone were delayed or reduced by continued exposure to a summer solstice photoperiod in autumn. The decreased photoperiod in autumn may thus influence the normal timing of the seasonal growth cycle.

Animals↗

Plasma glucose and insulin levels in genetically lean and fat sheep.

This study investigated whether genetically lean and fat sheep displayed differences in insulin and glucose statuses. Lean genotype sheep had significantly (P < 0.05) greater basal glucose concentrations than fat genotype sheep (4.78 versus 4.52, SED = 0. 104 mmol/l), although basal plasma insulin was not significantly different (mean 304, SEM = 37.3 pmol/l) between the genotypes. During glucose tolerance tests (GTT), carried out at 4 levels of injection: 0, 0.28, 1.39 or 2.78 mmol glucose/kg liveweight, the area under the plasma insulin curve was significantly (P < 0.05) greater for fat than lean genotype sheep, although there were no differences in any glucose parameters. There were no significant differences between genotypes in insulin or glucose concentrations during or following glucose infusion (GINF) experiments at 0, 0.09, 0.46 or 0.93 mmol glucose/kg live-weight/h over 3 hours. Elevated plasma insulin concentrations after a glucose tolerance test are concluded to be associated with increased fatness in this genetically selected line of sheep. However, the differences in insulin and glucose levels between the lean and fat genotype sheep are minor, relative to the differences in carcass composition.

Animals↗

Detection of growth factors and proto-oncogene mRNA in the growing tip of red deer (Cervus elaphus) antler using reverse-transcriptase polymerase chain reaction (RT-PCR).

Deer antler is a unique mammalian organ that has an annual cycle of regeneration. The antler grows very rapidly from the tip at up to 1 cm/day in red deer for a 90- to 120-day period. It is hypothesised that locally produced growth factors are required to control and stimulate this growth. The tip of the growing antler from animals whose antlers had been growing for 30, 60, or 90 days was dissected into four zones: epidermis/dermis, reserve mesenchyme, precartilaginous, and cartilaginous. Total RNA was extracted, and the presence of various growth factors and proto-oncogenes was detected using RT-PCR, IGF-I, IGF-II, TGF beta 1, TGF beta 2, c-fos, c-myc, and beta-actin were all present as single bands of the expected molecular weight in the four zones of the antler at each stage of growth. There were higher levels of IGF-I, TGF beta 2, and c-myc relative to beta-actin in the epidermis/dermis layer than in the other three zones. There were no differences in the expression of any of the genes between the three stages of growth. The presence of TGF beta 3 cannot be confirmed since multiple bands were seen in all antler tissues. A single band of the expected size for TGF alpha was seen only in the epidermal/dermal layer of the antler, with multiple bands of different molecular weight being detected in the other zones of the antler. This work has demonstrated the presence of multiple growth factors in the growing deer antler and supports the hypothesis that paracrine/autocrine stimulation is important for regulating antler growth.

Animals↗

Electron microscopic studies of antlerogenic cells from five developmental stages during pedicle and early antler formation in red deer (Cervus elaphus).

Previous studies using light microscopy have revealed that histogenesis of deer pedicle and antler has four ossification stages. The first of these stages is the development of the permanent pedicle. Initial development of the pedicle is from the cellular layer cells of the antlerogenic periosteum and these cells have been termed initial antlerogenic cells (IACs). Apart from the IACs, it has also been shown that the cellular layer cells of the apical periosteum/perichondrium, the peripheral periosteum of pedicles or antlers, and the marginal periosteum surrounding the pedicles are also capable of either partially or fully generating a pedicle or an antler. Therefore, these cells can all be considered antlerogenic cells and called apical antlerogenic cells (AACs), peripheral antlerogenic cells (PACs), and marginal antlerogenic cells (MACs), respectively. The aim of this study was to examine the ultrastructure of these antlerogenic cells, and to determine whether there were ultrastructural correlates with the changes of these antlerogenic cells and ossification stages. The ultrastructure of each type of antlerogenic cells was systematically examined using transmission electron microscopy, at each stage of pedicle and first antler growth. At the first ossification stage, the IACs were spindle-shaped and inactive. The most obvious feature was the presence of abundant intracellular glycogen. The MACs were similar to the IACs. During the early second stage, most of the AACs changed in appearance from preosteoblasts to prechondroblasts. Much less heterochromatin was found in the AACs than in the IACs. The most striking attribute of the AACs was the existence of intracellular collagen fibers. The MACs showed abnormal dilation of the rough endoplasmic reticulum (RER). During the late second stage, the majority of the AACs were prechondroblasts. AAC nucleoli were clearly discernible and the cisternae of the RER were arranged in parallel. The MACs contained a greater proportion of abnormally-dilated RER. During the third stage, the AACs were all prechondroblasts. The Golgi apparatus in these cells was well developed. Many free ribosomes in rosettes were scattered in the cytoplasm. Most cytoplasm of the majority of the MACs was occupied by abnormally-dilated RER (the lumen of the RER was extremely dilated and appeared electron-lucent). During the fourth stage, the AACs were similar to their counterparts from the third stage, but the boundaries of some AACs were ill-defined. Some MACs were found to be undergoing apoptosis. The PACs were becoming less and less active from distal to proximal along the shaft of the antler. It is a novel finding that antlerogenic cells change in appearance and subcellular content from preosteoblasts to prechondroblasts prior to the transition from intramembranous to endochondral ossification during pedicle formation. Therefore, the differentiation process from antlerogenic cells to chondroblasts is a matter of maturation from prechondroblasts to chondroblasts. The fact that the antlerogenic cells are rich in glycogen makes them more like embryonic cells. The local membrane deficiency of some AACs at the fourth stage and the presence of mature collagen fibrils within the AACs may reflect the unusually high demand for collagen fibrils during the period of rapid antler growth.

Animals↗

Expression of obese mRNA in genetically lean and fat selection lines of sheep.

Genetically separate lines of Coopworth sheep have been bred by selecting for (fat genotype) or against (lean genotype) backfat depth. Typically, the total fat content, adjusted for carcass weight, is 21.2 and 29.3% for the lean and fat lines, respectively. As a homologue of the obese gene, which shows altered expression in several forms of obesity, is also expressed in sheep, it was decided to determine whether the obese gene was differentially expressed in each line of sheep. The relative level of expression of obese mRNA was approximately twofold higher in the fat line compared with the lean line in back, omental and perirenal fat depots of ram lambs fed ad libitum or fasted for 48 h. This elevation in the fat line is most likely a secondary consequence of obesity rather than a cause. Fasting for 48 h decreased obese mRNA levels by 8.9-, 8.5-, and 4.2-fold in back, omental and perirenal fat, respectively, in the lean line, and by 8.3-, 5.7-, and 3.5-fold in back, omental and perirenal fat, respectively, in the fat line. The lean and fat lines of sheep, therefore, responded in a similar way to fasting.

Adipose Tissue↗

Prolactin does not enhance glucose-stimulated insulin release in red deer stags.

Red deer stags have a seasonal pattern of insulin secretion that is characterized by both elevated basal and glucose-stimulated insulin release in summer compared with winter. Since the seasonal timing of this pattern is similar to that of prolactin and growth rate, the objectives of this study were: first, to determine whether prolactin is associated with the enhanced secretion of insulin during the summer growth period, and second, to determine whether a chronic reduction in plasma prolactin levels would alter body composition. Prolactin was suppressed in plasma using a long-acting form of the dopamine agonist bromocriptine (parlodel LA), which was administered at one of four doses (0-0.3 mg/kg) to each of four groups of castrate stags. Bromocriptine was administered during two 6-wk periods; the first in winter and the second in summer. During the sixth wk of each period, each animal was given three IVGTT at the following glucose doses (10 mg/kg, 70 mg/kg, and 200 mg/kg). Two d later, ovine prolactin was administered to each animal (0.08 mg/kg) and a single IVGTT (70 mg/kg) was given 2 hr later. Body composition was determined by the tritriated water dilution method at the beginning and end of each 6-wk treatment. Chronic suppression of prolactin during winter or summer did not significantly alter the amount of insulin released after each IVGTT, nor did it significantly alter body composition. Furthermore, acute administration of prolactin did not significantly enhance the release of insulin following an IVGTT, during winter or summer treatment periods. It is concluded that elevated levels of prolactin in summer do not enhance the release of insulin to glucose in red deer. Furthermore, a reduction in growth rate following a reduction in plasma prolactin is not associated with a change in body composition.

Animals↗

The effects of a duplication in the ovine growth hormone (GH) gene on GH expression in the pituitaries of ram lambs from lean and fat-selected sheep lines.

Growth hormone (GH) gene expression was investigated in pituitaries of 14- to 15-month-old ram lambs from flocks selected for high (fat) or low (lean) back fat depth, which were also homozygous for a single GH gene allele, heterozygous or homozygous for a duplication in the GH gene. The pituitaries of lean sheep of all three GH genotypes were significantly heavier than those of fat sheep, but there were no pituitary weight differences between GH genotypes. No significant lean-fat selection line- or GH genotype-specific differences were measured in pituitary GH concentration. However there was a significant increase (P < 0.01) in the total pituitary content of GH in lean compared with fat animals and a significant interaction between GH genotype and lean-fat selection line (P < 0.05) was noted for GH content. No significant differences were measured in the relative concentration of GH mRNA, suggesting that the ratio of GH mRNA per mg total cellular RNA remained constant across lean-fat selection line and GH genotype. We conclude that the pituitary glands of Coopworth sheep selected for low backfat depth (lean) are bigger and have an increased GH content, but appear to contain similar concentrations of GH mRNA and immunoreactive GH as the pituitaries of fat sheep. The presence of the GH gene duplication in sheep has little measurable effect on the expression and storage of GH in the pituitary.

Alleles↗

The physiological effects of natural variation in growth hormone gene copy number in ram lambs.

The effects of natural variation in the number of copies of the growth hormone (GH) gene on growth parameters, plasma GH profiles, and the response to GHRH challenge were compared in Coopworth ram lambs from selection lines differing in body composition and GH levels. Different genotypes at the GH locus carried two, three, or four copies of the GH gene and GH secretion was studied under ad libitum feeding conditions and in the fasted state. There were no significant effects of GH genotype on any parameters of growth or body composition. Basal serum GH concentration, GH pulse frequency, and GH pulse amplitude differed significantly with selection line and fasting, but did not differ significantly between the GH genotypes. Significant differences of subtle nature were found between the GH genotypes in their responsiveness to GHRH. For the ad libitum-fed Lean selection line animals, the first GHRH challenge resulted in a higher mean maximum response for GH1/GH1 than GH2/GH2 (P < 0.05). Between the first and the second challenges there was a decrease in maximum response for the GH1/GH1 genotype and an increase for the GH2/GH2 genotype (P < 0.05 for GH genotype main effect). The differences between GH genotypes in response to GHRH challenge suggest that polymorphism in the number of GH gene copies in sheep may have physiological implications for the function of the GH axis, which may be manifested in growing lambs only under specific genotype-environment combinations.

Alleles↗