PubMed Health⌕ Search

Biomedical subjects

J A Mol

Publications and source records attributed to J A Mol.

At least 37 records · Page 2Linked to original sources
PubMed2002

Plasma concentrations of ACTH precursors correlate with pituitary size and resistance to dexamethasone in dogs with pituitary-dependent hyperadrenocorticism.

This study was performed to determine whether in dogs with pituitary-dependent hyperadrenocorticism (PDH) excessive release of adrenocorticotrophic hormone (ACTH) is accompanied by secretion of ACTH precursor molecules. In addition, we investigated whether the plasma ACTH precursor concentrations were correlated with the size of the pituitary gland and with the degree of resistance to negative glucocorticoid feedback. In 72 dogs with PDH, the plasma ACTH precursor concentration was determined by calculating the difference between the results of a radioimmunoassay (RIA) in which besides ACTH, ACTH precursors were also measured and a highly specific immunoradiometric assay (IRMA) using a polyclonal antibody against ACTH. The degree of resistance to glucocorticoid feedback was established by determining the effect of dexamethasone administration (0.1mg/kg) on the urinary corticoid/creatinine ratio. The pituitary height/brain area (P/B) ratio, determined by computed tomography, was used as a measure for the size of the pituitary gland. The plasma ACTH precursors concentration ranged from 18 to 2233ng/L (median 93ng/L). In 38 dogs, the pituitary was enlarged and plasma ACTH precursors concentrations in these dogs (median 130ng/L, range 24-2233ng/L) were significantly (P<0.05) higher than those in the dogs without pituitary enlargement (median 72ng/L, range 18-481ng/L). In concordance, P/B ratios correlated significantly with plasma ACTH precursor concentrations (r=0.35, P<0.01). In addition, the P/B ratios were significantly correlated with the degree of dexamethasone resistance (r=0.42, P<0.001). Plasma ACTH precursor concentrations in the dexamethasone-resistant dogs (median 210ng/L, range 24-628ng/L) were significantly higher (P<0.01) than those in the dexamethasone-sensitive dogs (median 72ng/L, range 18-2233ng/L). Similarly, the degree of dexamethasone resistance was also significantly correlated with the plasma ACTH precursor concentrations (r=0.33, P<0.01). Dogs with an elevated plasma alpha-MSH concentration (n=14) had significantly (P<0.001) higher plasma ACTH precursor concentrations (median 271ng/L, range 86-2233ng/L) than dogs with non-elevated alpha-MSH (median 73ng/L, range 18-481ng/L). In addition, the plasma concentrations of alpha-MSH correlated significantly with both plasma ACTH precursor concentrations (r=0.53, P<0.001) and P/B ratios (r=0.26, P<0.05). In conclusion, in all dogs with PDH the ACTH concentrations determined by the RIA were higher than the concentrations measured by IRMA indicating the presence of circulating ACTH precursors. High plasma ACTH precursor concentrations were especially found in dexamethasone-resistant dogs with large corticotroph adenomas, some of them probably of PI origin. In the association of large corticotroph adenoma, dexamethasone resistance and high plasma concentrations of ACTH precursors, the decreased sensitivity of the corticotroph cells to glucocorticoid feedback may play a pivotal role.

Adrenal Cortex↗
PubMed2002

Moderate cholecalciferol supplementation depresses intestinal calcium absorption in growing dogs.

Hormonal regulation of calcium (Ca) absorption was investigated in a cholecalciferol (vitamin D(3))-supplemented group (hVitD) vs. a control group (cVitD) of growing Great Danes (100 vs. 12.5 micro g vitamin D(3)/kg diet). Although Ca intakes did not differ, fractional Ca absorption was significantly lower in the hVitD group than in the cVitD group. There were no differences in plasma concentrations of Ca, inorganic phosphate, parathyroid hormone, growth hormone or insulin-like growth factor I between groups. Plasma 25-hydroxycholecalciferol [25(OH)D(3)] concentrations were maintained in the hVitD dogs at the same levels as in the cVitD dogs due to increased turnover of 25(OH)D(3) into 24,25-dihydroxycholecalciferol [24,25(OH)(2)D(3)] and 1,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)]. In hVitD dogs, the greater plasma 24,25(OH)(2)D(3) concentration and the enhanced metabolic clearance rate (MCR) of 1,25(OH)(2)D(3) indicated upregulated 24-hydroxylase activity. The increased MCR of 1,25(OH)(2)D(3) decreased plasma 1,25(OH)(2)D(3) concentrations. In hVitD dogs, the greater production rate of 1,25(OH)(2)D(3) was consistent with the 12.9-fold greater renal 1alpha-hydroxylase gene expression compared with cVitD dogs and compensated to a certain extent for the accelerated MCR of 1,25(OH)(2)D(3). The moderately decreased plasma 1,25(OH)(2)D(3) concentration can only partially explain the decreased Ca absorption in the hVitD dogs. Intestinal vitamin D receptor concentrations did not differ between groups and did not account for the decreased Ca absorption. We suggest that 24,25(OH)(2)D(3) may downregulate Ca absorption.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed2001

Immune response in hormonally-induced prostatic hyperplasia in the dog.

We induced prostatic enlargement in castrated dogs using either androgen alone or androgen combined with estrogen. In addition to previously reported hyperplastic changes, marked infiltration with immune effector cells was observed. This mononuclear cell infiltrate was phenotypically characterized using CD3 as pan T-lymphocyte marker, CD79 for B-lymphocytes, MAC378 for macrophages, and antibodies against kappa- and lambda-immunoglobulin (Ig) light chains for plasma cells. The majority of inflammatory cells (>80%) in the mononuclear infiltrates were T-lymphocytes and the numbers correlated with the degree of inflammation. The B-lymphocytes were found particularly in areas with marked follicular formation and diffuse infiltration, whereas there were only a few positive cells (<10%) in areas with a moderate or slight inflammation. Macrophages were found primarily in areas with atrophic and cystic changes with and without inflammation. The expression of lambda-Ig-positive cells depended on the degree of inflammation (5-10%), whereas immunoreactivity of kappa-Ig did not correlate with the extent of inflammatory reaction. Our present findings together with the evaluation of longitudinal biopsies of hormonally-induced BPH indicate that hyperplasia preceded cell-mediated and humoral immune response.

Androstane-3,17-diol↗
PubMed2001

Modulation of aggression in male mice: influence of group size and cage size.

Aggression in group-housed male mice is known to be influenced by both cage size and group size. However, the interdependency of these two parameters has not been studied yet. In this study, the level of aggression in groups of three, five, or eight male BALB/c mice housed in cages with a floor size of either 80 or 125 cm(2)/animal was estimated weekly after cage cleaning for a period of 14 weeks. Furthermore, urine corticosterone levels, food and water intake, body weight, and number of wounds were measured weekly. At the end of the experiment, tyrosine hydroxylase (TH) activity, testosterone levels, and weight of spleen, thymus, testes, and seminal vesicles were determined. Results indicate a moderate increase of intermale aggression in larger cages when compared to the smaller cages. Aggression in groups of eight animals was considerably higher than in groups of three animals. The increase of agonistic behavior was observed both in dominant and subordinate animals. Physiological parameters indicate differences in stress levels between dominant and subordinate animals. It is concluded that aggressive behavior in group-housed male BALB/c mice is best prevented by housing the animals in small groups of three to five animals, while decreasing floor size per animal may be used as a temporary solution to decrease high levels of aggression in an existing social group.

Aggression↗
PubMed2001

Aldosteronoma in a dog with polyuria as the leading symptom.

In a 10-year-old castrated male shorthaired German pointer polyuria was associated with slight hypokalemia, hypophosphatemia and alkalosis, as well as elevated plasma concentrations of a glucocorticoid-inducible iso-enzyme of alkaline phosphatase. Repeated measurements of urinary corticoids and normal suppressibility of the hypothalamus-pituitary-adrenocorticial axis excluded glucocorticoid excess. Urine osmolality (Uosm) did not increase during administration of the vasopressin analogue desmopressin. At the time water deprivation had caused Uosm to rise from 300 to 788 mOsm/kg, there was also plasma hypertonicity. During hypertonic saline infusion the osmotic threshold for vasopressin release was increased. The combination of elevated plasma aldosterone concentrations and unmeasurably low plasma renin activity pointed to primary hyperaldosteronism. As initially computed tomography (CT) did not reveal an adrenocortical lesion, the dog was treated with the aldosterone antagonist spironolactone. This caused Uosm to rise in a dose-dependent manner. However, well-concentrated urine was only achieved with doses that gave rise to adverse effects. Once repeated CT, using 2-mm-thick slices, had revealed a small nodule in the cranial pole of the left adrenal, unilateral adrenalectomy was performed which resolved the polyuria completely. Also the plasma concentrations of kalium, aldosterone and renin activity returned to within their respective reference ranges. The adrenocortical nodule had the histological characteristics of an aldosteronoma, with the non-affected zona glomerulosa being atrophic.In this dog with primary hyperaldosteronism the polyuria was characterized by vasopressin resistance and increased osmotic threshold of vasopressin release, similar to the polyuria of glucocorticoid excess. The possibility is discussed that the polyuria of glucocorticoid excess is actually a mineralocorticoid effect.

Adrenalectomy↗
PubMed2001

Primary hypothyroidism in dogs is associated with elevated GH release.

The pulsatile secretion patterns of GH were investigated in seven beagle bitches by collecting blood samples every 10 min for 6 h during euthyroidism and 1.5 years after induction of primary hypothyroidism. Hypothyroidism was induced by surgical removal of the thyroid gland and subsequent destruction of any remnant thyroid tissue by oral administration of sodium [(131)I]iodide. Some of the physical changes observed in the dogs with primary hypothyroidism mimicked those of acromegaly. During both euthyroidism and hypothyroidism GH was secreted in a pulsatile fashion. The mean (+/-s.e.m. ) basal plasma GH concentration was significantly higher (P=0.003) in the hypothyroid state (4.1+/-1.6 microg/l) than in the euthyroid state (1.2+/-0.4 microg/l). Likewise, the mean area under the curve (AUC) for GH above the zero-level during hypothyroidism (27.0+/-10.0 microg/lx6 h) was significantly higher (P=0.004) than that during euthyroidism (11.7+/-2.0 microg/l x 6 h). The mean AUC for GH above the baseline was significantly lower (P=0.008) during hypothyroidism (2.4+/-0.8 microg/l x 6 h) than during euthyroidism (4.5+/-1.8 microg/lx6 h), whereas there was no significant difference in GH pulse frequency. The mean plasma IGF-I level was significantly higher (P<0.01) in the hypothyroid state (169+/-45 microg/l) than in the euthyroid (97+/-15 microg/l). The results of this study demonstrate that primary hypothyroidism in dogs is associated with elevated basal GH secretion and less GH secreted in pulses. This elevated GH secretion has endocrine significance as illustrated by elevated plasma IGF-I levels and some physical changes mimicking acromegaly. It is discussed that the increased GH release in hypothyroid dogs may be the result of the absence of a response element for thyroid hormone within the canine pituitary GH gene and alterations in supra-pituitary regulation.

Animals↗
PubMed2001

Large body size in the dog is associated with transient GH excess at a young age.

The main determinants of body size are GH and IGFs. The aim of this study was to investigate whether differences in adult body size of medium-sized and giant dog breeds can be explained by differences in GH release and/or in plasma IGF-I and IGF-II concentrations at a young age. The basal plasma concentrations of GH, IGF-I and IGF-II were determined once weekly in six Great Danes and six beagles from the age of 6 weeks until the age of 24 weeks. In addition, the 6 h secretory profile of GH was determined every 2 weeks. Basal plasma GH concentrations as well as the total area under the curve (AUC) and the AUC above the baseline for GH were significantly higher in Great Danes than in beagles of the same age. In contrast, plasma IGF-I and IGF-II concentrations did not differ significantly between the two breeds. Compared with values in adults, the basal plasma GH concentrations were high until the age of 7 weeks in the beagles, whereas in the Great Danes the basal plasma GH levels remained high during the entire observation period, albeit with a gradual decline. The mean frequency and the mean amplitude of GH pulses tended to be higher in Great Danes than in beagles, although a significant difference was only reached at the age of 19 and 23 weeks for the frequency and at the ages of 9, 11 and 13 weeks for the amplitude. An age-dependent decrease in pulse frequency occurred in the Great Danes. The results of this study demonstrate that differences in adult body size of medium-sized and giant dog breeds are preceded by differences in GH release and not by differences in circulating IGF-I or IGF-II concentrations. Both young Great Danes and young beagles experience a period of high GH release, but this period persists much longer in Great Danes. It is discussed that this difference may be due to delayed maturation of the inhibitory influences of somatostatin on pituitary GH release in the latter dogs.

Animals↗
PubMed2000

Cloning and cellular localization of the canine progesterone receptor: co-localization with growth hormone in the mammary gland.

The mammary gland has been found to express the gene encoding growth hormone (GH) in several species. Within the mammary gland, it may act as an autocrine/paracrine growth factor for cyclic epithelial changes, and may be a determinant in mammary carcinogenesis. In the dog, progestins enhance mammary GH expression. To elucidate the mechanism of progestin-induced mammary GH expression, the canine progesterone receptor (PR) is characterized and the cellular localization of the PR in normal and tumorous mammary tissues is examined. Sequence analysis of the canine PR revealed two in-frame ATG codons, encoding a putative PR-B protein of 939 amino acids and a putative PR-A protein of 765 amino acids. Western blot analysis indicated that both isoforms occur in uterus and mammary gland issues. Immunohistochemical analysis of the PR revealed that the PR was differentially expressed in mammary tissue, with many PR-positive epithelial cells in the proliferation phase of the glandular tissue and a low number of PR-positive cells in differentiated mammary tissue. Stromal and myoepithelial cells had no specific PR staining. Mammary tumours had a variety of staining patterns, including no staining, normal nuclear staining, marked heterogeneous immunoreactivity and perinuclear staining of tumorous epithelial cells and cytoplasmic-staining of spindle cells. Double staining showed that all GH-producing cells were positive for PR, whereas not all PR containing cells stained for GH. It is concluded that the activated PR may transactivate GH expression in the mammary gland within the same cell and functions as a pre-requisite transcription factor. However, during malignant transformation this regulation may be lost.

Amino Acid Sequence↗
PubMed2000

Cell kinetics and differentiation after hormonal-induced prostatic hyperplasia in the dog.

BACKGROUND: Our aim was to characterize the immunophenotypical changes in canine prostate epithelium after hormonal-induced benign prostatic hyperplasia (BPH). METHODS: Castrated dogs (aged 1-2 and 9-12 years) were treated with vehicle (group C), androstanediol (group A), or androstanediol plus estradiol (group AE). Surgical prostate biopsies were obtained before and after castration and after hormonal treatment. Tissue sections were stained using antibodies specific for basal cells (34betaE12), transiently proliferating (TP)/amplifying cells (RCK103), and luminal exocrine cells (RGE53). RESULTS: Castration resulted in a marked reduction in specific immunoreactivity associated with luminal secretory cells and basal cells in young dogs. In older dogs the number of basal cells remained constant. Hormonal treatment (AE) resulted in an increased number of cells with an immunophenotype that was associated with the TP/amplifying cell compartment and hyperplastic luminal epithelium. CONCLUSIONS: The relative increase in TP/amplifying cells in hormonally induced BPH in the dog is in line with a stem-cell-derived proliferation. Moreover, the finding of androgen-independent basal cells in the prostate of older dogs may contribute to the enhanced risk of development of BPH with increasing age.

Age Factors↗
PubMed2000

Progestin-induced mammary growth hormone (GH) production.

Toxicity studies using beagle dogs revealed in the 1980s that synthetic progestins may induce a syndrome of growth hormone (GH) excess, known as acromegaly, and the development of predominantly benign mammary hyperplasia. In the early 1990s is was discovered that progestin-induced GH excess in the dog originates within the mammary gland. This mammary-derived GH may have endocrine, para/autocrine as well as exocrine effects. The expression of GH mRNA is also found in cats and humans indicating that mammary GH expression is not unique for the dog. The mammary gene is identical to the pituitary-expressed gene and uses the same promoter. Nevertheless a striking difference exists in the mammary gland. Pit-1, which is a prerequisite factor for pituitary GH mRNA expression, is likely not involved in the mammary gene expression. These studies shed new light on the mechanism of progesterone-induced mammary hyperplasia and urges for further research on potential adverse effects of synthetic progestins.

Animals↗
PubMed2000

Cloning of the canine gene encoding transcription factor Pit-1 and its exclusion as candidate gene in a canine model of pituitary dwarfism.

Combined pituitary hormone deficiency (CPHD) is an autosomal recessive inherited disease of German shepherd dogs characterized primarily by dwarfism. In mice and humans a similar genetic disorder has been described that results from an alteration in the gene encoding the transcription factor Pit-1. In this study we characterized the canine Pit-1 gene, determined the chromosomal localization of the Pit-1 gene, and screened dwarf German shepherd dogs for the presence of mutations in this gene. The full-length canine Pit-1 cDNA contained an open reading frame encoding 291 amino acids, 92 bp of 5'-untranslated region, and 1959 bp of 3'-untranslated region. The deduced amino acid sequence was highly homologous with Pit-1 of other mammalian species. Using a Pit-1 BAC clone as probe, the Pit-1 gene was mapped by FISH to canine Chromosome (Chr) 31. In dwarf German shepherd dogs a C to A transversion was detected, causing a Phe (TTC) to Leu (TTA) substitution at codon 81. This alteration was present neither in other canine breeds analyzed nor in other mammalian species. However, healthy German shepherd dogs were also homozygous for the mutant allele, indicating that it is not the primary disease-causing mutation. In addition, linkage analysis of polymorphic DNA markers flanking the Pit-1 gene, 41K19 and 52L05, revealed no co-segregation between the Pit-1 locus and the CPHD phenotype. These findings suggest that a gene other than Pit-1 is responsible for the pituitary anomaly in dwarf German shepherd dogs.

Amino Acid Sequence↗
PubMed2000

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.

Adrenocorticotropic Hormone↗
PubMed2000

Secretion pattern of thyroid-stimulating hormone in dogs during euthyroidism and hypothyroidism.

In as many as one third of dogs with primary hypothyroidism a plasma thyrotropin (TSH) concentration within the reference range for euthyroid dogs is found. To determine whether this is due to fluctuations in the release of TSH, the plasma profiles of TSH were analyzed in 7 beagle bitches by collecting blood samples every 10 min for 6 hr, both before and after induction of primary hypothyroidism. After induction of primary hypothyroidism, a 37-fold increase in mean basal plasma TSH concentration and a 34-fold increase in mean area under the curve for TSH were found. Analysis by the Pulsar program demonstrated pulsatile secretion of TSH in the hypothyroid state, characterized by relatively low amplitude pulses (mean [+/-SEM]) amplitude 41 +/- 3% of basal plasma TSH level) and a mean pulse frequency of 2.0 +/- 0.5 pulses/6 hr. In the euthyroid state, significant TSH pulses were identified in only 2 dogs. The mean basal plasma TSH level correlated positively (r = 0.84) with the mean amplitude of the TSH pulses, and correlated negatively (r = -0.88) with the TSH pulse frequency. The results of this study demonstrate pulsatile secretion of TSH in dogs during hypothyroidism and only small fluctuations in plasma TSH concentrations during euthyroidism. The findings also suggest that the low TSH values occasionally found in dogs with spontaneous primary hypothyroidism may in some cases in part be the result of ultradian fluctuations.

Animals↗
PubMed2000

Cloning, characterization, and physical mapping of the canine Prop-1 gene (PROP1): exclusion as a candidate for combined pituitary hormone deficiency in German shepherd dogs.

Abnormalities in the genes encoding Pit-1 and Prop-1 have been reported to cause combined pituitary hormone deficiency (CPHD) in mice and humans. In dogs, a similar phenotype has been described in the German shepherd breed. We have previously reported that the Pit-1 gene (POU1F1) is not mutated in affected German shepherd dogs. In this study, we report the isolation and mapping of the canine Prop-1 gene (PROP1), and we assessed the involvement of PROP1 in German shepherd dog dwarfism. The canine PROP1 gene was found to contain three exons, encoding a 226 amino acid protein. The deduced amino acid sequence was 79% and 84% homologous with the mouse and human Prop-1 protein, respectively. Using fluorescence in situ hybridization, PROP1 was mapped to canine chromosome 11. Further mapping with a canine radiation hybrid panel showed co-localization with the polymorphic DNA marker AHT137. Sequence analysis of genomic DNA from dwarf German shepherd dogs revealed no alterations in the PROP1 gene. Moreover, linkage analysis of AHT137 revealed no co-segregation between the PROP1 locus and the CPHD phenotype, excluding this gene as candidate for canine CPHD and providing a new spontaneous model of hypopituitarism.

Amino Acid Sequence↗
PubMed2000

Pulsatile secretion pattern of growth hormone during the luteal phase and mid-anoestrus in beagle bitches.

The pulsatile secretion pattern of growth hormone was investigated during four stages of the luteal phase and during mid-anoestrus in six cyclic beagle bitches. Plasma samples were obtained via jugular venepuncture at 10 min intervals for 12 h at 19 +/- 2 (mean +/- SEM; luteal phase 1), 38 +/- 2 (luteal phase 2), 57 +/- 2 (luteal phase 3), 78 +/- 2 (luteal phase 4) and 142 +/- 4 days (mid-anoestrus) after ovulation. During all stages, growth hormone was secreted in a pulsatile fashion. The mean basal plasma growth hormone concentration during luteal phase 1 (2.2 +/- 0.3 microgram l(-1)) was significantly higher than that during luteal phase 4 (1.5 +/- 0.1 microgram l(-1)) and mid-anoestrus (1.4 +/- 0.2 microgram l(-1)). The mean area under the curve (AUC) above zero during luteal phase 1 (27.3 +/- 2.7 microgram l(-1) in 12 h) tended to be higher than that during luteal phase 4 (20.8 +/- 1.8 microgram l(-1) in 12 h) and mid-anoestrus (19.2 +/- 2.5 microgram l(-1) in 12 h). In contrast, the mean AUCs above the baseline during luteal phase 1 (1.1 +/- 0.5 microgram l(-1) in 12 h) and luteal phase 2 (1.2 +/- 0.5 microgram l(-1) in 12 h) were significantly lower than that during luteal phase 4 (2.8 +/- 0.5 microgram l(-1) in 12 h). In conclusion, the pulsatile secretion pattern of growth hormone changes during the luteal phase in healthy cyclic bitches: basal growth hormone secretion is higher and less growth hormone is secreted in pulses during stages in which the plasma progesterone concentration is high. It is hypothesized that this change is caused by a partial suppression of pituitary growth hormone release by progesterone-induced growth hormone production in the mammary gland. The progesterone-induced production of growth hormone in the mammary gland may promote the physiological proliferation and differentiation of mammary gland tissue during the luteal phase of the bitch by local autocrine-paracrine effects. In addition, progesterone-induced mammary growth hormone production may exert endocrine effects, such as hyperplastic changes in the uterine epithelium and insulin resistance.

Anestrus↗
PubMed1999

Canine mammary growth hormone gene transcription initiates at the pituitary-specific start site in the absence of Pit-1.

Growth hormone (GH) gene expression has been reported in the mammary glands of various mammalian species. The mechanism by which the GH gene becomes activated in extrapituitary tissues is currently unclear. We have characterized the canine mammary and pituitary GH gene transcripts by Northern blot, 5'- and 3'-RACE (rapid amplification of cDNA ends), and DNA sequence analysis. Northern blot analysis detected GH gene transcripts in mammary glands of dogs which were exposed to high levels of progestins. The mammary and pituitary GH cDNAs were shown to be identical in both the coding region and untranslated regions. Pituitary GH gene expression is highly dependent upon the transcription factor Pit-1. Analysis of Pit-1 gene expression using RT-PCR followed by Southern hybridization revealed a strong pituitary signal but faint, weak or no hybridization signals in mammary gland samples. Among the negative samples were progestin-treated dogs with high mammary GH gene expression. These findings indicate that mammary and pituitary GH gene transcripts originate from the same transcription start site but are regulated differentially.

Amino Acid Sequence↗