Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endocrine system coordinates development of the mammary gland with reproductive development and the demand of the offspring for milk. Three categories of hormones are involved. The levels of the reproductive hormones, estrogen, progesterone, placental lactogen, prolactin, and oxytocin, change during reproductive development or function and act directly on the mammary gland to bring about developmental changes or coordinate milk delivery to the offspring. Metabolic hormones, whose main role is to regulate metabolic responses to nutrient intake or stress, often have direct effects on the mammary gland as well. The important hormones in this regard are growth hormone, corticosteroids, thyroid hormone, and insulin. A third category of hormones has recently been recognized, mammary hormones. It currently includes growth hormone, prolactin, PTHrP, and leptin. Because a full-term pregnancy in early life is associated with a reduction in breast carcinogenesis, an understanding of the mechanisms by which these hormones bring about secretory differentiation may offer clues to the prevention of breast cancer.
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PMID:Hormonal regulation of mammary differentiation and milk secretion. 1216 86

Galactogogues are medications that aid in initiating and maintaining adequate milk production. Most exert their pharmacologic effects through interactions with dopamine receptors, resulting in increased prolactin levels and thereby augmenting milk supply. Metoclopramide remains the galactogogue of choice due to its documented record of efficacy and safety in women and infants. Domperidone crosses the blood brain barrier and into the breast milk to a lesser extent than metoclopramide, decreasing the risk of toxicity to both mother and infant possibly making it an attractive alternative. Traditional antipsychotics, sulpiride and chlorpromazine, have been evaluated, but adverse events limit their use. Human growth hormone, thyrotrophin-releasing hormone, and oxytocin have also been studied. Finally, a natural product, fenugreek, has been purported to be effective in anecdotal reports. Use of this agent may be warranted after considering risks versus benefits.
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PMID:Galactogogues: medications that induce lactation. 1219 64

In order to fulfill their roles in neuroendocrine regulation, specific hypothalamic neurons are devoted to produce and deliver biologically active peptides to the pituitary gland. The biosynthesis and release of peptides are strictly controlled by afferents to these hypothalamic neurons. Cell-specific expression and biosynthetic regulation largely relies on transcription from the gene promoter for which the 5(')-flanking regions of the peptidergic genes contain essential elements. Cell-specific transcription factors employ these regulatory elements to exert their control over the expression of the peptidergic gene. This article explores the properties of regulatory elements of the major hypothalamic peptides, somatostatin, growth hormone-releasing hormone, gonadotropin-releasing hormone, thyrotropin-releasing hormone, corticotropin-releasing hormone, vasopressin and oxytocin, and the transcription factors acting on them. These transcription factors are often endpoints of signal transduction pathways that can be activated by neurotransmitters or steroid hormones. Others are essential to provide cell-specific expression of the peptidergic gene during development and mature regulation.
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PMID:Regulation of gene promoters of hypothalamic peptides. 1238 30

This study investigated the influence of chronic hyperthyroidism on mammary function in lactating rats and the effects on their pups. Thyroxine-treated (10 microg per 100 g body weight per day; hyperthyroid (HT)) or vehicle-treated rats were mated 2 weeks after the start of treatment and killed with their litters on days 7, 14 and 21 of lactation. Serum concentrations of triiodothyronine (T(3)) and tetraiodothyronine (T(4)) increased in thyroxine-treated rats. In HT mothers, serum prolactin decreased on day 7 and day 14 of lactation, whereas insulin-like growth factor I (IGF-I) and progesterone concentrations decreased, and corticosterone increased on day 7 of lactation. In HT pups, T(4) concentration increased on day 7 and day 14 of lactation, whereas T(3) increased only on day 14 of lactation, and growth hormone increased on day 7 of lactation. Mammary prolactin binding sites did not vary, but there was an increase in the binding sites in the liver on day 14 of lactation in thyroxine-treated rats. In an acute suckling experiment, thyroxine-treated rats released less oxytocin, growth hormone and prolactin and excreted less milk than did control rats. Mammary casein, lactose and total lipid concentrations in thyroxine-treated rats were similar to those of control rats on day 14 of lactation. Histological studies of the mammary glands showed an increased proportion of alveoli showing reduced or no lumina and cells with condensed nuclei on day 14 and day 21 of lactation; the TdT-mediated dUTP nick-end labelling (TUNEL) test revealed an increase in apoptosis in alveolar cells on day 21 of lactation in thyroxine-treated rats. Expression of SGP-2, a gene expressed during mammary involution, increased in thyroxine-treated rats on day 14 and day 21 of lactation, whereas expression of insulin-like growth factor binding protein 5, a proapoptotic signal, was unchanged. Bcl-2, which promotes survival of mammary gland epithelial cells was unchanged, whereas expression of IGF-I, which also promotes survival of mammary gland epithelial cells, increased on day 21 of lactation in thyroxine-treated rats. These results indicate that thyroxine treatment produces some milk stasis as a result of impairments in suckling induced release of oxytocin that may initiate the first stage of mammary involution, increasing apoptosis in a gland that is otherwise actively producing and secreting milk.
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PMID:Hyperthyroidism and production of precocious involution in the mammary glands of lactating rats. 1241 8

This study evaluated the effect of different milking managements on oxytocin, prolactin and growth hormone release in Gir x Holstein cows. Six cows were suckled by their calves, before and after milking (SM group); another six cows were submitted to exclusive milking (M group). High OT levels were observed during suckling of the SM group, however both groups had similar levels of OT during milking. The SM group presented PRL levels significantly higher than the M group, however only during suckling. For GH levels, the SM group showed higher levels than the M group, however this difference was significant only during the first suckling, cleaning of the teats and at the beginning of machine milking. Despite these results, SM cows produced more milk (milking plus suckling) than M cows, however milk obtained by milking was similar for both groups.
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PMID:Effect of calf suckling on oxytocin, prolactin, growth hormone and milk yield in crossbred Gir x Holstein cows during milking. 1251 Aug 77

A group of oxytocinergic neurons originating in the paraventricular nucleus of the hypothalamus and projecting to extrahypothalamic brain areas (e.g. hippocampus, medulla oblongata and spinal cord) control penile erection. Activation of these neurons by dopamine and dopamine agonists, excitatory amino acids (N-methyl-D-aspartic acid) or oxytocin itself, or by electrical stimulation leads to penile erection, while their inhibition by GABA and GABA agonists or by opioid peptides and opiate-like drugs inhibits this sexual response. The activation of oxytocinergic neurons in the paraventricular nucleus by dopamine, oxytocin and excitatory amino acids is apparently secondary to the activation of nitric oxide (NO) synthase. NO in turn activates, by a mechanism that is as yet unidentified, the release of oxytocin from oxytocinergic neurons in extrahypothalamic brain areas. Several peptide analogues of hexarelin, a growth hormone releasing peptide, also induce penile erection when injected into the paraventricular nucleus and, to a lesser extent, systemically, apparently by acting on a specific receptor to activate oxytocinergic neurons as shown for the above drugs and oxytocin. Paraventricular oxytocinergic neurons and mechanisms similar to those reported above are also involved in the expression of penile erection in physiological contexts, namely when penile erection is induced in the male by the presence of an inaccessible receptive female, which is considered a model for psychogenic impotence in man, as well as during copulation. These findings show that paraventricular oxytocinergic neurons projecting to extra-hypothalamic brain areas and to the spinal cord are a likely target for the treatment of erectile dysfunction of central origin.
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PMID:Central oxytocinergic neurotransmission: a drug target for the therapy of psychogenic erectile dysfunction. 1252 90

The pituitary has been called the master gland of the body because of its central role in governing homeostasis, maintaining the reproductive cycle, and directing the activity of other glands. Housed in the sella turcica of the sphenoid bone at the base of the skull, it has important anatomic relations with the hypothalamus, visual pathways, cavernous sinus, carotid artery, and cranial nerves. The gland originates from two discrete parts of the developing embryo. Rathke's pouch, a dorsal evagination of the stomodeum, forms the anterior and intermediate lobes. The infundibulum, a ventral extension of the diencephalon, forms the posterior lobe. The anterior, intermediate, and posterior lobes of the pituitary gland function as three separate endocrine organs, each characterized by distinct cell populations, secretory products, and regulatory mechanisms. The anterior lobe secretes thyroid stimulating hormone, corticotropin, luteinizing hormone, follicle stimulating hormone, growth hormone, and prolactin. It is regulated by the hypothalamus via the portal vascular system. The posterior lobe releases oxytocin and vasopressin from axon terminals that originate in cell bodies located in the hypothalamus. The intermediate lobe is rudimentary in human beings but produces several hormones whose physiologic significance is only now being established.
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PMID:Pituitary anatomy and physiology. 1269 Sep 76

Neuropeptides play an important role in the regulation of feeding behavior and obesity. The mechanisms for controlling food intake involve a complicated interplay between peripheral systems (including gustatory stimulation, gastrointestinal peptide secretion, and vagal afferent nerve responses) and central nervous system (CNS) neuropeptides and/or monoamines. These neuronal systems include neuropeptides (CRH, opioids, neuropeptide-Y (NPY) and peptide YY (PYY), vasopressin and oxytocin, CCK, and leptin) and monamines (serotonin, dopamine, norepinephrine). In addition to regulating eating behavior, a number of CNS neuropeptides participate in the regulation of neuroendocrine pathways. Thus, clinical studies have evaluated the possibility that CNS neuropeptide alterations may contribute to dysregulated secretion of the gonadal hormones, cortisol, thyroid hormones and growth hormone in the eating disorders. Most of the neuroendocrine and neuropeptide alterations apparent during symptomatic episodes of AN and BN tend to normalize after recovery. This observation suggests that most of the disturbances are consequences rather than causes of malnutrition, weight loss and/or altered meal patterns. Still, an understanding of these neuropeptide disturbances may shed light on why many people with AN or BN cannot easily "reverse" their illness and even after weight gain and normalized eating patterns, many individuals who have recovered from AN or BN have physiological, behavioral and psychological symptoms that persist for extended periods of time.
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PMID:A review of neuropeptide and neuroendocrine dysregulation in anorexia and bulimia nervosa. 1276 12

Human growth hormone (hGH) and bovine neurophysin (bNP) DNA reporter fragments were inserted into the rat vasopressin (VP) and oxytocin (OT) genes in a 44 kb cosmid construct used to generate two lines of transgenic rats, termed JP17 and JP59. Both lines showed specific hGH expression in magnocellular VP cells in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON). hGH was also expressed in parvocellular neurones in suprachiasmatic nuclei (SCN), medial amygdala and habenular nuclei in JP17 rats; the rat OT-bNP (rOT-bNP) transgene was not expressed in either line. Immunohistochemistry and radioimmunoassay showed hGH protein in the hypothalamus from where it was transported in varicose fibres via the median eminence to the posterior pituitary gland. Immunogold electron microscopy showed hGH co-stored with VP-NP in the same granules. The VP-hGH transgene did not affect water balance, VP storage or release in vivo. Drinking 2 % saline for 72 h increased hypothalamic transgene hGH mRNA expression, and depleted posterior pituitary hGH and VP stores in parallel. In anaesthetised, water-loaded JP17 rats, hGH was released with VP in response to an acute hypovolumic stimulus (sodium nitrosopentacyano, 400 microg I.V.). JP17 rats had a reduced growth rate, lower anterior pituitary rGH contents, and a reduced amplitude of endogenous pulsatile rGH secretion assessed by automated blood microsampling in conscious rats, consistent with a short-loop feedback of the VP-hGH on the endogenous GH axis. This transgenic rat model enables us to study physiological regulation of hypothalamic transgene protein production, transport and secretion, as well as its effects on other neuroendocrine systems in vivo.
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PMID:Transgenesis and neuroendocrine physiology: a transgenic rat model expressing growth hormone in vasopressin neurones. 1281 55

Thyroid dysfunctions can produce reproductive problems. Untreated maternal hypothyroidism has serious consequences on development of offspring, resulting in stunted growth and mental retardation. The effects of propylthiouracyl-induced hypothyroidism (0.1 g l(-1) in drinking water starting 8 days before mating, or given to virgin rats for 30 or 50 days) on the serum profiles of hormones related to reproduction and mammary function (prolactin, growth hormone (GH), progesterone, corticosterone, oestradiol, insulin-like growth factor I (IGF-I), thyroid-stimulating hormone (TSH), triiodothyronine and tetraiodothyronine), and on mammary function in virgin, pregnant and lactating rats, were investigated. Propylthiouracyl treatment severely decreased circulating triiodothyronine and tetraiodothyronine concentrations, and increased serum TSH concentrations. Virgin rats showed prolonged periods of vaginal dioestrus, increased circulating progesterone concentrations and afternoon peaks of prolactin concentration, which are indicative of prolactin-induced pseudopregnancy. Propylthiouracyl-treated virgin rats had mammary development comparable to that of midpregnancy, and half of these rats had increased mammary casein and lactose concentrations. Serum prolactin concentrations were decreased on the afternoon of day 5 of pregnancy, increased during late pregnancy (days 15-21) and were normal during lactation. Circulating GH concentrations decreased on days 15-21 of pregnancy, whereas progesterone concentrations increased during late pregnancy and early lactation. Circulating oestradiol (measured in late pregnancy and in virgin rats), IGF-I and corticosterone concentrations were decreased. Although assessment of mammary histology showed no differences in extent of development, casein content was increased in propylthiouracyl-treated rats on day 21 of pregnancy; litter growth was severely reduced and at day 20 of age the pups were hypothyroid, with decreased GH serum concentrations. An acute suckling experiment was performed on days 10-12 of lactation to determine whether some impairment in mammary function or the suckling reflex might account for these differences. After an 8 h separation of mothers from their litters and 30 min of suckling, circulating prolactin values were not affected by propylthiouracyl treatment, but serum oxytocin concentration and milk excretion were reduced. In conclusion, hypothyroidism induces various alterations in the hormone profiles of virgin and pregnant rats, and induces pseudopregnancies and mammary development in virgin rats. These alterations do not appear to have an overt impact on the outcome of pregnancy and on mammary function during lactation, with the exception of the milk ejection reflex, which may account at least partially for the reduced litter growth.
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PMID:Effect of hypothyroidism on hormone profiles in virgin, pregnant and lactating rats, and on lactation. 1296 45


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