Hypothalamic control of the thyroidal axis in the chicken: over the boundaries of the classical hormonal axes

The pituitary gland, occupying a central position in the hypothalamo-pituitary thyroidal axis, produces thyrotropin (TSH), which is known to stimulate the thyroid gland to synthetize and release its products, thyroid hormones. TSH is produced by a specific cell population in the pituitary, the so-called thyrotropes. Their secretory activity is controlled by the hypothalamus, releasing both stimulatory and inhibitory factors that reach the pituitary through a portal system of blood vessels. Based on early experiments in mammals, thyrotropin-releasing hormone (TRH) is generally mentioned as the main stimulator of the thyrotropes. During the past few decades, it has become clear that the hypophysiotropic function of the hypothalamus is more complex, with different hormonal axes interacting with each other. In the chicken, it was found that not only TRH, but also corticotropin-releasing hormone (CRH), the main stimulator of corticotropin release, is a potent stimulator of TSH secretion. Somatostatin (SRIH), a hypothalamic factor known for its inhibitory effect on growth hormone secretion, was demonstrated to blunt the TSH response to TRH and CRH. In this review we summarize the latest studies concerning the "interaxial" hypothalamic control of TSH release in the chicken, with a special emphasis on the molecular components of these control mechanisms. It remains to be demonstrated if these findings could also be extrapolated to other species or classes of vertebrates.     

Suppression of somatotroph function induced by growth hormone treatment in neonatal pigs

The effect of recombinant porcine growth hormone (pGH) treatment on pituitary function was evaluated in young pigs. Piglets received intraperitoneal recombinant pGH implants (0.5 mg/d sustained release) or vehicle implants beginning at 3 d of age. Ten piglets were sacrificed at 4 and 6 wk of age (five piglets/treatment group) for the collection of pituitary glands, blood, and liver tissue. Blood samples also were drawn at 3 and 12 d of age. Serum concentrations of GH, prolactin (PRL), thyroid-stimulating hormone (TSH), insulin-like growth factor-1 (IGF-1) and IGF-2 were evaluated. Levels of IGF-1 and IGF-2 mRNA were determined in liver samples. Treatment with GH increased circulating levels of GH and IGF-1 (P < 0.01), but not PRL, TSH, or IGF-2. Hepatic IGF-1, but not IGF-2, mRNA levels were increased by pGH (P < 0.001). Cultured pituitary cells from each animal were challenged with 0.1, 1, and 10 nM GH-releasing hormone (GHRH); 2 mM 8-Br-cAMP; or 100 nM phorbol myristate acetate. The release of GH from cultured pituitary cells was stimulated by all secretagogues (P < 0.001). The secretion of GH, but not PRL or TSH, in culture was inhibited by previous in vivo GH treatment (P < 0.001). Similarly, cellular GH, but not PRL or TSH, content was lower in the GH-implant group (P = 0.005). Cell cultures from 6-wk-old piglets secreted more GH, but not PRL or TSH, than cultures from 4-wk-old piglets (P < 0.05). Likewise, cellular GH, but not PRL or TSH, content was greatest in cultures from 6-wk-old animals (P = 0.002). Piglet growth was not affected by exogenous GH treatment (P = 0.67). These results demonstrate that exogenous pGH treatment selectively down-regulates somatotroph function in young pigs.     

Adenohypophyseal Function in Dogs with Primary Hypothyroidism and Nonthyroidal Illness

Background: A recent study of dogs with induced primary hypothyroidism (PH) demonstrated that thyroid hormone deficiency leads to loss of thyrotropin (TSH) hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with large vacuolated "thyroid deficiency" cells that double-stained for growth hormone (GH) and TSH, indicative of transdifferentiation of somatotropes to thyrosomatropes.
Hypothesis: Similar functional changes in adenohypophyseal function occur in dogs with spontaneous PH as do in dogs with induced PH, but not in dogs with nonthyroidal illness (NTI).
Animals: Fourteen dogs with spontaneous PH and 13 dogs with NTI.
Methods: Adenohypophyseal function was investigated by combined intravenous administration of 4 hypophysiotropic releasing hormones (4RH test), followed by measurement of plasma concentrations of ACTH, GH, luteinizing hormone (LH), prolactin (PRL), and TSH. In the PH dogs this test was repeated after 4 and 12 weeks of thyroxine treatment.
Results: In 6 PH dogs, the basal TSH concentration was within the reference range. In the PH dogs, the TSH concentrations did not increase with the 4RH test. However, TSH concentrations increased significantly in the NTI dogs. Basal and stimulated GH and PRL concentrations indicated reversible hypersomatotropism and hyperprolactinemia in the PH dogs, but not in the NTI dogs. Basal and stimulated LH and ACTH concentrations did not differ between groups.
Conclusions and Clinical Importance: Dogs with spontaneous PH hypersecrete GH but have little or no TSH hypersecretion. Development of hyperprolactinemia (and possible galactorrhea) in dogs with PH seems to occur only in sexually intact bitches. In this group of dogs with NTI, basal and stimulated plasma adenohypophyseal hormone concentrations were not altered.     

Combined pituitary hormone deficiency in german shepherd dogs with dwarfism

In German shepherd dogs pituitary dwarfism is known as an autosomal recessive inherited abnormality. To investigate whether the function of cells other than the somatotropes may also be impaired in this disease, the secretory capacity of the pituitary anterior lobe (AL) cells was studied by a combined pituitary AL stimulation test with four releasing hormones (4RH test) in four male and four female German shepherd dwarfs. In addition, the morphology of the pituitary was investigated by computed tomography. The physical features of the eight German shepherd dwarfs were primarily characterized by growth retardation and stagnant development of the hair coat. The results of the 4RH test confirmed the presence of hyposomatotropism. The basal plasma TSH and prolactin concentrations were also low and did not change upon stimulation. Basal plasma concentrations of LH were relatively low and responded only slightly to suprapituitary stimulation. With respect to the plasma FSH levels there was a clear gender difference. In the males plasma FSH concentrations remained below the detection limit throughout the 4RH test, whereas in the females the basal plasma FSH levels were slightly lower and there was only a small increase following suprapituitary stimulation, compared with the values in age-matched controls. In contrast, basal and stimulated plasma ACTH concentrations did not differ between the dwarfs and the controls. Computed tomography of the pituitary fossa revealed a normal sized pituitary with cysts in five dogs, an enlarged pituitary with cysts in two dogs, and a small pituitary gland without cysts in the remaining dog. The results of this study demonstrate that German shepherd dwarfs have a combined deficiency of GH, TSH, and prolactin together with impaired release of gonadotropins, whereas ACTH secretion is preserved. The combined pituitary hormone deficiency is associated with cyst formation and pituitary hypoplasia.     

Female infertility in grt mice is caused by thyroid hormone deficiency, not by insufficient TPST2 activity in the reproductive organs

The growth-retarded (grt) mouse has an autosomal recessive hypothyroidism and the female shows lifelong infertility. We previously reported that these mutant phenotypes are caused by a deficiency in the enzymatic activity of tyrosylprotein sulfotransferase-2 (TPST2), and severe thyroid hypogenesis and consequent dwarfism are mainly due to the impairment of the tyrosine sulfation of thyroid-stimulating hormone receptor (TSHR) by TPST2. Although TPST2 is ubiquitously expressed and many proteins are predicted to be tyrosine sulfated and involved in many biological processes, the functional roles of tyrosine sulfation in the reproductive organs remain unclear. These findings tempted us to hypothesize two possible mechanisms underlying the infertility; a deficiency in TPST2 activity in the reproductive organs might cause the infertility in grt mice, or a significant decrease in serum thyroid hormones might impair the normal development of reproductive organs. When mutant female mice were fed a diet supplemented with sufficient thyroid powder to correct their growth retardation, the rate of copulation, pregnancy, and parturition was completely restored. Therefore, we concluded that the infertility in grt female is due to a thyroid hormone deficiency.     

The relationship between insulin-like growth factor-1, growth hormone, thyroid hormones and insulin in chickens selected for growth

The concentrations of circulating insulin-like growth factor I, growth hormone, insulin and thyroid hormones were measured in broilers selected for an increase in growth, broilers in which selection pressure was relaxed and in White Leghorns. Growth hormone levels increased in all lines between 3 and 4 weeks of age followed by a decline to adult levels. The lines with the slowest rate of growth had the highest growth hormone concentrations. Insulin-like growth factor I concentrations increased significantly in all three lines of birds during the 10 weeks of study and was significantly correlated with the increase in body weight. There were no consistent differences in plasma IGF-1 levels between the lines. Thyroxine levels increased consistently throughout the study but the levels of triiodothyronine decreased between 5 and 6 weeks of age in all lines. There were no consistent changes in plasma insulin levels. The highest rate of growth in these animals is accompanied by an increase in growth hormone concentration followed by an increase in plasma IGF-1. However, despite differences in plasma growth hormone, plasma concentrations of IGF-1 are not different between lines and are not related to between line differences in growth rate.     

Application of the peroxidase-antiperoxidase procedure to the localization of pituitary hormones and calcitonin in various domestic animals and human beings

Specific cell populations in the pituitary glands of the rat, cat, pig, and human being were positive for thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). When reacted with prediluted rabbit anti-human TSH, LH, and FSH, antisera were not positive for the demonstration of these hormones in the horse, cow, or dog. Immunocytochemical staining was obtained in the horse, cow, and dog by the use of a primary antiserum against a specific beta-subunit of bovine TSH. The immunocytochemical staining of TSH, LH, FSH, adrenocorticotropic hormone, growth hormone, prolactin, and calcitonin was examined by the peroxidase-antiperoxidase method, using standard commercially available kits. All species examined had a strong positive reaction in specific pituitary cell populations for adrenocorticotropic hormone, growth hormone, and prolactin. Sections of normal thyroid gland tissue had positive staining of C cells containing calcitonin at the dilution of 1:100 of the primary antibody in the rat, horse, cow, dog, cat, pig, and human being.     

Thyroid function tests in euthyroid dogs treated with L-thyroxine

The effects of treatment with L-thyroxine (1 mg/m2 of body surface/d, PO, for 8 weeks) on the thyroxine (T4) and triiodothyronine (T3) responses to thyrotropin (TSH) and thyrotropin-releasing hormone (TRH) administration were determined in 10 euthyroid Beagles; 4 other dogs acted as controls. The TSH response test was performed before treatment and at weeks 2, 4, and 8 of treatment in all dogs and at 2 and 4 weeks after cessation of treatment in 6 dogs. The TRH response test was performed before treatment and at week 6 of treatment in all dogs and at 5 weeks after cessation of treatment in 6 dogs. Suppression of the T3 response to TSH was evident at treatment week 2, whereas the T4 response was suppressed at week 4 and remained suppressed for the duration of the study. Four weeks after stopping treatment, T4 and T3 responses to TSH in 2 dogs were within the hypothyroid range. The T4 response to TRH was completely suppressed after 6 weeks of thyroxine treatment, but returned to pretreatment values by 5 weeks after cessation of treatment. Suppression of thyroid and pituitary function is evident after administration of a replacement dose of L-thyroxine to euthyroid dogs.     

Quantitative morphologic study of the pituitary and thyroid glands of dogs administered L-thyroxine.

To determine the effects of long-term thyroxine treatment, histomorphometric analysis was performed on the pituitary and thyroid glands of healthy dogs, dogs treated for 9 weeks with a replacement dose of L-thyroxine, and dogs at 6 weeks after cessation of thyroxine treatment. In treated dogs, the volume density of thyrotropes decreased during thyroxine treatment and increased 6 weeks after cessation of treatment, compared with thyrotropes of healthy nontreated dogs. The activity of the thyroid gland was decreased in dogs during thyroxine treatment, as evidenced by decreases in epithelial volume density, epithelial height, and follicular area, and increase in colloid volume density, compared with thyroid gland activity in nontreated dogs. After cessation of thyroxine treatment, the thyroid gland had decreased colloid area, follicular area, and epithelial volume density, and increased interstitial volume density, compared with the thyroid gland of healthy nontreated dogs. Thyroxine treatment resulted in suppression of pituitary thyrotropes and thyroid follicular activity.     

Effects of delmadinone acetate on pituitary-adrenal function, glucose tolerance and growth hormone in male dogs

Objective To characterise the effects of delmadinone acetate on the pituitary-adrenal axis, glucose tolerance and growth hormone concentration in normal male dogs and dogs with benign prostatic hyperplasia.
Design A prospective study involving nine normal male dogs and seven with prostatic hyperplasia.
Procedure Delmadinone acetate was administered to six normal male dogs and seven dogs with benign prostatic hyperplasia at recommended dose rates (1.5 mg/kg subcuta-neously at 0, 1 and 4 weeks). Three normal controls received saline at the same intervals. Blood concentrations of ACTH, cortisol, glucose, insulin and growth hormone were measured over 50 days. Intravenous glucose tolerance and ACTH response tests were performed before and after treatment in the nine normal animals.
Results A substantial suppression of basal and 2 h post-ACTH plasma cortisol secretion was demonstrated after one dose in all dogs given delmadinone acetate. Individual responses after the second and third administration varied between recovery in adrenal responsiveness to continued suppression. Plasma ACTH concentration was also diminished after one treatment. No effects were evident on glucose tolerance or serum growth hormone concentrations.
Conclusion Delmadinone acetate causes adrenal suppression from inhibition of release of ACTH from the pituitary gland. Treated dogs may be at risk of developing signs of glucocorticoid insufficiency if subjected to stressful events during or after therapy. Neither glucose intolerance nor hyper-somatotropism seems likely in male dogs given delmadinone acetate at the recommended dose rate, but the potential for excessive growth hormone secretion in treated bitches remains undetermined.     

Effects of thyrotropin-releasing hormone and a thyrotropin releasing hormone analog on growth and selected plasma hormones in lambs

An 8-wk growth trial was conducted to assess the effects of continuous infusion of thyrotropin-releasing hormone (TRH) and an active TRH analog less than Aad-His-Pro-NH2 (the less than Aad is L-pyro-alpha-aminoadipic acid) on growth trial performance, carcass composition and hormone profiles of growing lambs. Both drugs were infused at 600 micrograms X lamb -1 X d -1 with 16 lambs/treatment. Both TRH and less than Aad-His-Pro-NH2 decreased average daily gain (ADG; P less than .01) and increased feed conversion (FC; P less than .01) compared with saline infused controls. Average daily feed intake was not altered. Carcasses of lambs given TRH or less than Aad-His-Pro-NH2 contained fewer kilograms of moisture (P less than .05) and appeared to contain fewer kilograms of protein. Thyrotropin-releasing hormone and less than Aad-His-Pro-NH2 increased thyroid gland weights (P less than .05), but pituitary gland weights were not different. Plasma thyrotropin (TSH) concentrations were increased by both drugs compared with control lambs, peaking at 4 to 7 d after initiating infusion. However, by 14 d, TSH concentrations returned to control levels. Triiodothyronine (T3) and thyroxine (T4) were elevated by both drugs over the entire 8-wk trial, with peak levels reached at 10 d and maintained for the duration of the study. Both TRH and less than Aad-His-Pro-NH2 increased prolactin over the entire period. Growth hormone levels were not altered by either drug. The effects of less than Aad-His-Pro-NH2 infusion on growth trial performance, carcass composition and hormone profiles of growing lambs were very similar to TRH. The negative effects of TRH and less than Aad-His-Pro-NH2 infusion on ADG, FC and carcass protein appear to be the result of elevated T3 and T4 levels.     

Segmentation of the Pathophysiological Stages of Diabetic Changes in the db/db Mouse

The db/db mouse is one of the diabetes mellitus animal models and if the pathophysiological stages of diabetic changes in the mouse model could simulate the stages in human diabetes, the db/db mouse could be used to better evaluate drug candidates. Blood insulin, HbA1c levels and morphological features of pancreatic islets in db/db mice were evaluated to determine the pathophysiological stage. At 6 weeks of age, db/db mice showed the highest level of plasma insulin and lowest level of HbA1c, and histopathological examination revealed enlarged islets with a circular shape and hypertrophic islet cells. By 9 and 12 weeks of age, the plasma insulin levels had decreased to mid levels and HbA1c had increased to mid to high levels; histopathological examination at this time revealed two types of islets coexisting, enlarged circular islets and small irregular-shaped islets. By 15 and 22 weeks of age, plasma insulin had decreased further to low levels and HbA1c was at its highest level; the histopathological examination at this time revealed an increase in irregular-shaped and small islets. Based on blood insulin levels, HbA1c levels and histopathology findings in the db/db mice in this study, the clinical staging of diabetic changes were recognized. The pathophysiological stages of diabetes mellitus in this animal model were similar to the stages in humans.     

Histologic pattern of testicular regrowths in caponized tom turkeys.

Testicular regrowths were observed in 10 of 21 tom turkeys between 28 and 32 weeks old, which was between 19 and 23 weeks after surgical caponization at 9 weeks of age. Regrowths were not observed in younger caponized toms. Two types of histologic patterns that differed from the normal pattern were observed in these regrowths. The first pattern was observed in seven regrowths and was characterized by a higher density of seminiferous tubules and more interstitial cells. The second pattern was seen in three regrowths and was characterized by extensive intertubular fibrosis, tubular detachment, and an increased number of interstitial cells. No correlation was found between the presence of these regrowths and plasma testosterone levels. The interstitial cell hyperplasia in all regrowths possibly was related to a diminished negative feedback by the endogenous testosterone on the release of luteinizing hormone from the pituitary. The appearance of regrowths at this age probably was related to the onset of normal physiological puberty.     

Effect of recombinant bovine tumor necrosis factor-α on hormone release in lactating cows

Tumor necrosis factor (TNF)‐α is a powerful macrophage cytokine released during infection, circulating in the blood to produce diverse effects in the organism. We examined the effect of recombinant bovine TNF‐α (rbTNF‐α) administration on hormone release in dairy cows during early lactation. Twelve non‐pregnant Holstein cows were treated subcutaneously with rbTNF‐α (2.5 µg/kg) or saline twice (at 11.00 and 23.00 hours). At 11.00 hours the next day, the cows were given growth hormone‐releasing hormone (GHRH, 0.25 µg/kg), thyrotrophin‐releasing hormone (TRH, 1.0 µg/kg), thyroid‐stimulating hormone (TSH, 10 µg/kg) or adrenocorticotropic hormone (500 µg/head) via the jugular vein. In the growth hormone‐releasing hormone challenge, the plasma growth hormone concentration was lower in the rbTNF‐α group than in the control (saline) group. The growth hormone and TSH responses to TRH were also smaller in the rbTNF‐α group than in the control. The plasma prolactin response to TRH was not affected by the rbTNF‐α treatment. In the TSH challenge, the rbTNF‐α‐treated cows had lower responses, as measured by plasma triiodothyronine and thyroxine, than the control cows. The rbTNF‐α treatment produced an increase in the basal plasma cortisol level, but the cortisol response to adrenocorticotropic hormone was the same level in both groups. The plasma concentrations of TNF‐α and interleukin‐1β in the cows were elevated by the rbTNF‐α treatment. The milk yield was reduced by the rbTNF‐α administration during 4 days. These data demonstrate that TNF‐α alters the secretion of pituitary and thyroid hormones in lactating cows. This effect may contribute to the suppression of the lactogenic function of the mammary gland observed in cases of coliform mastitis with high circulating TNF‐α levels.     

植物甾醇对KM雌性小鼠生长及生殖激素的影响

本试验旨在研究植物甾醇对雌性小鼠生长及生殖激素的影响。选用50只35日龄雌性小鼠,适应1周后随机分为5组,分别为：对照组、植物油组（给予0.1 mL植物油）及植物甾醇低、中、高三个剂量组（每日灌胃20、80和320 mg/kg植物甾醇）。连续灌胃3周,第1天和第22天称取小鼠体重,然后眼球采血,制备血清,对小鼠血清中的雌二醇、孕酮、催乳素水平进行检测,研究不同添加量的植物甾醇对小鼠生长及生殖激素的影响。结果显示：与对照组相比,植物油组小鼠体增重差异显著（P＜0.05）。与植物油组相比,植物甾醇处理组小鼠体增重先升高后降低,但差异不显著（P＞0.05）。植物甾醇对小鼠血清E2水平有不同程度的提高,其中中剂量组小鼠的雌二醇水平最高（270.52＆#177;18.10 pmol/L）;随着植物甾醇灌胃剂量的增加,小鼠孕酮水平都有不同程度的下降,其中植物甾醇中剂量组小鼠血清孕酮水平显著低于对照组（P＜0.05）。植物甾醇灌胃组小鼠催乳素水平与对照组相比,差异不显著（P＞0.05）。表明低剂量植物甾醇可提高KM雌性小鼠的体增重;植物甾醇能提高KM雌性小鼠血清雌二醇水平,但对孕酮和催乳素的作用不显著。     

Regulation of pituitary somatotroph differentiation by hormones of peripheral endocrine glands

Anterior pituitary somatotroph differentiation occurs during chick embryonic and rat fetal development. A number of findings support the hypothesis that differentiation of these growth hormone (GH) producing cells in the chick and the rat is regulated by adrenal glucocorticoids and thyroid hormones. Somatotroph differentiation can be induced in cultures of chick embryonic and rat fetal pituitary cells with adrenal glucocorticoids and this effect can be modulated by concomitant treatment with thyroid hormones. Plasma levels of thyroid hormones, corticosterone and adrenocorticotropic hormone increase during development, consistent with the ontogeny of somatotrophs. Treatment of chick embryos or rat fetuses with glucocorticoids in vivo induces premature somatotroph differentiation, indicating that the adrenal gland, and ultimately anterior pituitary corticotrophs, may function to regulate pituitary GH cell differentiation during development. Administration of thyroid hormones in vivo also increases somatotrophs prematurely, and administration of the thyroid hormone synthesis inhibitor methimazole inhibits somatotroph differentiation in vivo, suggesting that endogenous thyroid hormone synthesis contributes to normal somatotroph differentiation. Our working model for the regulation of somatotroph differentiation during normal development includes modulation by elements of the hypothalamo-pituitary-adrenal and hypothalamo-pituitary-thyroid axes. Additional research is reviewed defining the mechanism of action for these peripheral hormones in induction of pituitary GH gene expression during development.     

Regulation of growth hormone expression by thyrotropin-releasing hormone through the pituitary-specific transcription factor Pit-1 in chicken pituitary

Pit-1 is a pituitary-specific POU-domain DNA binding factor, which binds to and trans-activates promoters of growth hormone- (GH), prolactin- (PRL) and thyroid stimulating hormone beta- (TSHbeta) encoding genes. Pit-1 has been identified in several mammalian and avian species. Thyrotropin-releasing hormone (TRH) is located in the hypothalamus and it stimulates TSH, GH and PRL release from the pituitary gland. In the present study, we successfully developed a competitive RT-PCR for the detection of Pit-1 expression in the chicken pituitary, that was sensitive enough to detect picogram levels of Pit-1 mRNA. Applying this method, the effect of TRH injections on Pit-1 mRNA expression was determined in the pituitary of chick embryos and growing chicks. In both 18-day-old embryos and 10-day-old male chicks the Pit-1 mRNA expression was significantly increased following TRH injection, thereby indicating that the stimulatory effects of TRH on several pituitary hormones is mediated via its effect on Pit-1 expression. Therefore, a semi-quantitative RT-PCR method was used to detect possible changes in GH levels. TRH affected the GH mRNA levels at both developmental stages. These results, combined with the data on Pit-1 mRNA expression, indicate that Pit-1 has a role in mediating the stimulatory effects of TRH on pituitary hormones like GH.     

Immunohistochemical observations on TSH secreting cells in pituitary glands of goat kids with congenital goitre

Pituitary glands of normal-termed stillborn goat kids with congenital goitre and normal-termed stillborn goat kids without congenital goitre were examined macroscopically, histopathologically and immunohistochemically. Thyroid glands of these animals were also examined grossly and microscopically. The pituitary glands of kids with goitre were larger than those of normal kids, and on histopathological examination there was hyperplasia of the acidophil cells in the ventral part of the glands. However, it was impossible to distinguish thyroid stimulating hormone (TSH)-secreting cells from other acidophil cells in sections stained with haematoxylin and eosin (HE). Red granules were observed in the cytoplasm of these hyperplastic cells in periodic acid-Schiff (PAS)-stained sections. Sections were also immunostained with an antibody against TSH using the streptavidin-biotin peroxidase technique. Immunohistochemistry revealed TSH-secreting cells to have increased in number in the pituitary glands of kids with congenital goitre because of the extensive proliferation when compared with those of normal kids. The present study indicated that the presence of multiple fetuses (twins or triplets) may be a predisposing factor for congenital goitre.     

Comparative Aspects of the Endotoxin- and Cytokine-Induced Endocrine Cascade Influencing Neuroendocrine Control of Growth and Reproduction in Farm Animals

Disease in animals is a well-known inhibitor of growth and reproduction. Earlier studies were initiated to determine the effects of endotoxin on pituitary hormone secretion. These studies found that in sheep, growth hormone (GH) concentration was elevated, whereas insulin-like growth factor-I (IGF-I) was inhibited, as was luteinizing hormone (LH). Examination of the site of action of endotoxin in sheep determined that somatotropes expressed the endotoxin receptor (CD14) and that both endotoxin and interleukin-Iβ activated GH secretion directly from the pituitary. In the face of elevated GH, there is a reduction of IGF-I in all species examined. As GH cannot activate IGF-I release during disease, there appears to be a downregulation of GH signalling at the liver, perhaps related to altered nitration of Janus kinase (JAK). In contrast to GH downregulation, LH release is inhibited at the level of the hypothalamus. New insights have been gained in determining the mechanisms by which disease perturbs growth and reproduction, particularly with regard to nitration of critical control pathways, with this perhaps serving as a novel mechanism central to lipopolysaccharide suppression of all signalling pathways. This pathway-based analysis is critical to the developing novel strategies to reverse the detrimental effect of disease on animal production.