Mẹo Which of the following best explains the presence of prolactin in various vertebrate species?
Kinh Nghiệm về Which of the following best explains the presence of prolactin in various vertebrate species? Chi Tiết
Hoàng Trung Dũng đang tìm kiếm từ khóa Which of the following best explains the presence of prolactin in various vertebrate species? được Cập Nhật vào lúc : 2022-09-08 22:44:01 . Với phương châm chia sẻ Kinh Nghiệm về trong nội dung bài viết một cách Chi Tiết Mới Nhất. Nếu sau khi Read nội dung bài viết vẫn ko hiểu thì hoàn toàn có thể lại phản hồi ở cuối bài để Admin lý giải và hướng dẫn lại nha.Hyperprolactinemia
Nội dung chính- HyperprolactinemiaBiochemistry and Physiology of ProlactinGene and Protein VariantsEndocrinology of Fetal DevelopmentGrowth Hormone and ProlactinProlactin variantsAnterior Pituitaryc) PropertiesCarbohydrate Metabolism and AdiposityMolecular and Cellular EndocrinologyIntroductionWhat is the function of prolactin in females quizlet?Which of the following observations provides the best evidence that acetyl CoA negatively regulates?
Rick D. Kellerman MD, in Conn's Current Therapy 2022, 2022
Biochemistry and Physiology of Prolactin
Prolactin is a polypeptide hormone produced by pituitary lactotroph cells. It is also produced locally in a variety of extrapituitary tissues such as mammary glands, decidua, gonads, brain, liver, fat, pancreas, and the immune system, along with its receptors. Prolactin is highly pleiotropic in terms of its functions. Many of its actions collectively support puerperal lactation. Prolactin displays considerable sequence homology to growth hormone (GH) and placental lactogen. The prolactin and GH receptors both belong to the class I cytokine/hematopoietic receptor superfamily. Prolactin is responsible for maturation of the mammary glands during pregnancy, but it plays only a minor role for pubertal mammary development, which requires GH instead. It appears not to be an essential hormone for non-childbearing individuals. Rare patients deficient for either prolactin or its receptor are largely healthy despite difficulty with fertility and lactation.
Prolactin circulates mainly as a 23-kDa 199-aa polypeptide. Several of its cleavage products exist in blood, which may have functions unrelated to lactation; for example, one 16-kDa cleavage product of prolactin displays antiangiogenic and prothrombotic properties, and has been implicated in the development of preeclampsia and peripartum cardiomyopathy. Several forms of prolactin aggregate, known as macroprolactins, also exist in circulation lower levels. They are formed either by covalent bonding of prolactin monomers or by their nucleating around autoimmune IgG. These macroprolactins are not biologically active in vivo and have a prolonged half-life. At times they can build up in the circulation to a level high enough to cause diagnostic difficulties.
Among the major pituitary hormones, prolactin is unique for its predominantly negative mode of regulation by the hypothalamus. It does not have a known hypothalamus-derived releasinghormone. Instead, lactotrophs are under tonic inhibition by dopamine secreted from hypothalamic neurons. Increase in prolactin output is mostly mediated by withdrawing dopaminergic control in response to environmental cues, such as physical activity, stress, and nipple stimuli (Figure 1). Under experimental and pathological conditions, several factors, including thyrotropin-releasing hormone (TRH), vasoactive intestinal peptide (VIP), oxytocin, and vasopressin, have been shown to increase prolactin secretion, but these peptides appear to play only minor and insignificant roles for the physiological regulation of prolactin.
Estrogen is the main driver of prolactin secretion during pregnancy. Stimulated by persistently elevated estrogen, lactotrophs grow in number and size. By term the pituitary gland can reach 2 to 3 times its normal size, and prolactin levels increase some 20-fold. Along with placental hormones such as estrogen, progesterone, and placental lactogen, prolactin drives the maturation of the mammary glands. Lactation starts after parturition, when estrogen withdraws from the circulation. Frequent infant suckling maintains physiological hyperprolactinemia, which is important for sustained milk production. In addition, hyperprolactinemia during this critical period provides a natural though unreliable way of contraception. This is achieved by suppression of the hypothalamus–pituitary–gonad axis. Hyperprolactinemic hypogonadism and parathyroid hormone related peptide (PTHrP) secreted from mammary epithelial cells help mobilize skeletal calcium store in support of milk production. Through its receptors in liver, intestine, fat, and pancreas prolactin also adjusts maternal nutrient metabolism for optimal milk output. In the brain, prolactin modifies parental behavior toward closer infant attendance (seeFigure 1).
Prolactin
Kiyohito Mizutani, Yoshimi Takai, in Reference Module in Biomedical Sciences, 2022
Gene and Protein Variants
Prolactin is a peptide hormone, which is encoded by the PRL gene on chromosome 6 in human (Truong et al., 1984). The human prolactin cDNA contains a 681-nucleotide open reading frame, thereby producing a precursor protein with 227 amino acids. After a cleavage of the 28 amino acid signal peptide, the mature 23 kDa human prolactin is produced. Although the 23 kDa prolactin is the major variant, other variants with its molecular mass of 14, 16, and 22 kDa are also characterized. These variants are generated from proteolytic cleavage of the 23 kDa prolactin (Freeman et al., 2000). A high-resolution NMR solution structure of human prolactin revealed that the core of the human prolactin structure is made up by four major α-helices (Teilum et al., 2005).
Read full chapter
URL: https://www.sciencedirect.com/science/article/pii/B9780128012383980188
Endocrinology of Fetal Development
Shlomo Melmed MB ChB, MACP, in Williams Textbook of Endocrinology, 2022
Growth Hormone and Prolactin
The fetal pituitary gland can synthesize and secrete GH by 8 to 10 weeks’ gestation. Pituitary GH content increases from about 1 nmol (20 ng) 10 weeks to 45 nmol (1000 ng) 16 weeks. Fetal plasma GH concentrations in cord blood samples are in the range of 1 to 4 nmol/L during the first trimester and increase to a mean peak of approximately 6 nmol/L in midgestation. Plasma GH concentrations fall progressively during the second half of gestation, to a mean value of 1.5 nmol/L term.57 The responses of plasma GH to somatostatin and GHRH and to insulin and arginine are mature term in human infants.57,153 The high plasma GH concentrations after development of the pituitary portal vascular system midgestation may reflect unrestrained secretion.57 Whatever the mechanisms, control of GH secretion matures progressively during the last half of gestation and the early weeks of postnatal life, so that mature responses to sleep, glucose, and l-dopa are present by 3 months of age. GH secretion is already pulsatile soon after birth in humans,154 but trough concentrations are still higher than in later life so that random GH sampling can be used to detect GH deficiency in the neonatal period, which is not possible a later age.155
The ontogenesis of fetal plasma PRL differs significantly from that of GH; concentrations are low until 25 to 30 weeks’ gestation and increase to a mean peak value of approximately 11 nmol/L term (Fig. 23.5).57 Pituitary PRL content increases progressively from 12 to 15 weeks. PRL release increases in response to TRH and decreases in response to dopamine. Brain and hypothalamic control of PRL matures late in gestation and during the first months of extrauterine life.57,153 The marked increase in fetal plasma PRL concentration in the last trimester parallels the increase in fetal plasma estrogen concentrations, although it lags by several weeks.57,153
Postnatally, GH acts through receptors in liver and other tissues to stimulate production of IGF1 and, to a lesser degree, IGF2. Prenatally, GH receptor mRNA levels and receptor binding are low in fetal liver, although receptor messenger ribonucleic acid (mRNA) is present in other fetal tissues.57 The growth of anencephalic fetuses is almost normal, suggesting that factors other than GH stimulate fetal IGF production. Nutrition plays an important role.156,157 PRL receptors are present in most fetal tissues during the first trimester of gestation, and it is likely that lactogenic hormones have a significant role in organ and tissue development early in gestation.61,157
Prolactin
Hallgeir Rui, Marja T. Nevalainen, in The Cytokine Handbook (Fourth Edition), 2003
Prolactin variants
Prolactin circulates in blood as monomers of 23–26 kDa (Lewis et al., 1985). In addition, larger ‘macroprolactins’ (big-prolactin, big-big prolactin) represent both homo-oligomeric aggregates and immunoglobulin-complexed prolactin (Sinha, 1995). In certain asymptomatic subjects with hyperprolactinemia stable circulating complexes between immunoglobulin and prolactin have been identified (Bonhoff et al., 1995; Hattori and Inagaki, 1998), suggesting that anti-prolactin autoantibodies may occasionally neutralize the activity of hormone. Furthermore, physiological proteolysis of prolactin yields an N-terminal16 kDa variant with distinct biological activities, and that activates a unique, yet-to-be identified receptor (Mittra, 1980; Clapp and Weiner, 1992; Clapp et al., 1993; D'Angelo et al., 1999).
Read full chapter
URL: https://www.sciencedirect.com/science/article/pii/B9780126896633500107
Anterior Pituitary
Lee Goldman MD, in Goldman-Cecil Medicine, 2022
Prolactin
Both prolactin and growth hormone have similar amino acid sequences and are present in all vertebrates. During pregnancy, prolactin concentrations increase and, in conjunction with the other hormones of pregnancy, stimulate the breast epithelium to produce milk. Lactotrophs, which are the cells that secrete prolactin, represent 20 to 50% of the anterior pituitary cell population and are the most likely to give rise to pituitary tumors. Prolactin is now implicated in not only lactation, but also inhibition of reproductive function (by suppression of gonadotropins) and support of maternal behavior. The function is less clear when prolactin is expressed outside the pituitary, including in the mammary gland and uterine decidua. A prolactin variant, “big prolactin” or macroprolactin, is a high-molecular-weight variant due to the tendency of prolactin to aggregate and form intermolecular disulfide bridges spontaneously or with IgG. Despite their immunoreactivity, these prolactin variants usually have decreased biologic activity.
Prolactin binds to the prolactin receptor, which is a thành viên of the type 1 cytokine receptor family. Janus kinase-2 is a protein kinase that is associated with the prolactin receptor and mediates prolactin’s effect in the target cells in ways that are incompletely understood. The prolactin receptor is also the receptor for placental lactogens, which are hormones synthesized during pregnancy and which are also a result of prolactin or growth hormone gene duplication.
Regulation of prolactin secretion by lactotrophs is primarily under the inhibition of dopamine, which acts through the D2-type receptors on lactotrophs. Inhibition of the dopamine (“inhibiting the inhibitor”) results in a release of prolactin as is seen in nonsecreting pituitary tumors or trauma that disrupts the pituitary stalk, thereby preventing dopamine from inhibiting prolactin release. Estrogen is a potent stimulator of lactotroph proliferation and raises the possibility that exogenous estrogen could increase the growth of prolactinomas, although clinical evidence suggests this phenomenon may be true only for macroprolactinomas. Thyrotropin releasing hormone (TRH) and vasoactive intestinal peptide (VIP) also stimulate the release of prolactin, so when hypothyroidism increases TRH release from the hypothalamus, it causes hyperprolactinemia. In addition to the hypothalamic control, prolactin secretion is induced by sleep, stress, chest wall stimulation, and pregnancy. During pregnancy, high levels of estrogen and progesterone inhibit lactation, and their postpartum decline permits lactation accompanied by the secretion of oxytocin in response to suckling.
Prolactin DeficiencyThe normal concentration for prolactin is less than 15 to 20 pg/mL in women and less than 10 to 15 pg/mL in men. The consequences of low prolactin values and the lower limits of normal are not well understood, but the limit of detection of prolactin in most clinical assays is less than 1 pg/mL. Low serum levels of prolactin can be seen in hyperthyroidism because TRH is suppressed. Low prolactin may prevent adequate lactation in nursing mothers and may be a reliable marker for hypopituitarism when seen with another pituitary hormone deficiency. Lactation is not completely absent because nipple stimulation may be sufficient to start milk production. No cases of isolated prolactin deficiency have been reported in men.
Prolactin
F.G. Sulman, in Hypothalamic Control of Lactation, 1970
c) Properties
Prolactin has been prepared in a highly purified form from ox and sheep pituitaries. Isolation procedures have been described by Li (1961) in a review on the biochemistry of prolactin. The physical properties of sheep (198 aminoacids) and ox (205 aminoacids) prolactin are remarkably similar. The hormone from both species has a molecular weight of 24,000 to 26,000, an isoelectric point pH 5.73, and a sedimentation constant of 2.19. Dixon and Li (1964) showed that the hormone molecule consists of a single peptide chain with one không lấy phí amino acid group, but no không lấy phí carboxy end-group. They suggested that the peptide chain has an intra-chain disulfide bridge forming a ring similar to that present in vasopressin and oxytocin. The results of their structural studies are summarized in the following schematic representation of prolactin:
H2N-Thr1−Pro2− Val3−Thr4−Pro5−(CyS)4−(CyS)Tyr202−Leu-203Asp 204(NH2)−CyS205-COOH.
In order to investigate aggregation and charge differences between prolactin components, a combination of gel filtration, ion-exchange chromatography, and zone electrophoresis was used by Sluyser and LI (1964). As a result of these investigations, a method was developed for the isolation of monomer prolactin in highly purified form. The experiments presented in their paper show that the various peaks or bands which appear when prolactin is submitted to either ion exchange chromatography or zone electrophoresis are due to the presence of molecular aggregates in the preparations. The degree of aggregation differed from batch to batch. Some prolactin preparations contained about 20% monomer whereas others had a much lower content of unassociated material. In view of the reported finding that some aggregation of prolactin can occur when solutions are submitted to lyophilization, pervaporation, sucrose concentrates, or extremes of pH, it seems likely that the differences in degree of aggregation between various batches of lactogenic hormone arise least partly during the preparation of the samples. In order to prevent aggregation, the hormone solution was concentrated by chromatography on small columns of DEAE-cellulose. A separation was achieved between fractions representing different states of polymerization of prolactin molecules. One of the fractions contained monomer prolactin, as revealed by exclusion chromatography and sedimentation equilibrium experiments. The molecular weight of monomer prolactin was estimated to be 23,000.
Prolactin is not soluble in any fat solvent. It is, however, soluble in water, except in the isoelectric region pH 5—6, and in strongly acid solution. It may be salted out with sodium or ammonium sulfate or sodium chloride, the required amount depending on the pH. It is also precipitated by basic salts of heavy metals or near pH 7. It is rapdily inactivated by trypsin and pepsin. Salt-không lấy phí solutions pH 8 withstand boiling for one hour with only negligible loss; under other conditions, prolactin may be rapidly destroyed. Frozen preparations are not stable, once they have been thawed.
Despite the great similarities of bovine and ovine prolactin, certain differences have been observed. It seems that, proportionate to weight, ovine prolactin is more active than bovine prolactin. There is less tyrosine in ovine prolactin, and distribution of the two hormones in countercurrent analysis is different. However, Bryant and Greenwood (1968) showed by radioimmunoassay of blood that ovine prolactin antigen can substitute for bovine prolactin. Human prolactin has yet to be characterized, but the fact that methods effective for isolating ox and sheep prolactin have completely failed when applied to human pituitaries suggests that primate prolactin may have peculiarities of structure which make it very similar to human growth hormone.
Read full chapter
URL: https://www.sciencedirect.com/science/article/pii/B978043328991350007X
Prolactin
Mary P. Gillam, Mark E. Molitch, in The Pituitary (Third Edition), 2011
Carbohydrate Metabolism and Adiposity
PRL functions as a metabolic regulator in two chief areas: (1) pancreatic β cell development and function; (2) appetite regulation and adiposity. The phenotypic assessment of Prlr-/- mice indicates that signaling through the PRLR, which serves as a common receptor for both PL and PRL, is important to fully attain normal β cell mass, insulin content and insulin secretory capacity [456]. The PRLR plays a particularly central role in the adaptation of islets to pregnancy, as illustrated by studies in heterozygous Prlr+/- female mice. Pregnant female mice haploinsufficient for PRLR exhibit impaired glucose clearance, reduced glucose-stimulated insulin release and lower insulin levels as a result of impaired islet expansion [457]. In support of the critical role of PRLR for islet expansion during gestation, it has been shown that Stat 5, PI3 kinase, MAPK and pathways involving the endocrine tumor suppressor menin all collaborate to mediate the proliferative effects of PRL and PL on pancreatic islets during pregnancy [458–460]. Treatment of mice with PRL also increases feeding behavior, raising the possibility that PRLRs both in the islet and the brain contribute to islet adaptation to pregnancy [461]. Although studies in humans are limited, in vitro experiments confirm that PRL increases β cell number and stimulates insulin secretion in cultured human islets [462,463].
With regard to appetite regulation and adiposity, in vivo studies in rodents and humans support a modest orexigenic effect of PRL. In rats, higher PRL levels are associated with greater food intake and body toàn thân weight, while suppression of PRL levels leads to the opposite effects [323,464]. Likewise, injection of PRL into the paraventricular nucleus of the hypothalamus increases food intake [465]. PRLR-deficient mice exhibit a subtle reduction in parametrial and subcutaneous adipose tissue mass as compared to wild-type littermates, although no differences are observed in overall body toàn thân weight [466]. PRL-deficient mice exhibit normal body toàn thân weight and adiposity [467], suggesting that PLs or other ligands act in conjunction with PRL to influence adiposity. In humans, normal circulating PRL levels do not appear to modulate energy homeostasis; however, hyperprolactinemia has been shown to be associated with mild glucose intolerance, increases in body toàn thân weight and insulin resistance [468,469]. Treatment with a DA agonist to normalize prolactin lowers glucose levels and induces weight loss in these individuals [468,469]. In contrast to these results, suppression of PRL levels with bromocriptine has no effect on glycemic control in normoprolactinemic subjects with insulin-dependent diabetes [470]. A new preparation of bromocriptine, which has been approved in the US for the treatment of diabetes [471], has been shown to cause a modest reduction in plasma glucose and hemoglobin A1c levels. However, the safety of lowering normal PRL levels to subnormal levels, with respect to fertility and sexual function, has not been proven.
Other in vitro studies suggest a possible role for PRL in adipogenesis. PRL itself is produced in small amounts by human adipocytes, including sources from the breast, visceral and subcutaneous adipose tissue [472]. The PRLR is expressed in both brown and white adipose tissue [472,473]. PRL up-regulates the mRNA expression of its receptor and two transcription factors that are principally involved in adipocyte differentiation, CEBP/β and PPARγ [474], and it also stimulates the conversion of NIH-3T3 fibroblasts into adipocytes. Complex interactions between PRL and several adipokines, such as leptin and adiponectin, have been described. However, the data regarding the effects of exogeneous PRL, transgenic overexpression of PRL, and PRL deficiency on leptin levels in vivo are inconsistent and preclude reliable conclusions [475]. Studies addressing the relationship between PRL and adiponectin levels have mostly shown inhibitory effects. PRL injections into mice inhibit adiponectin release [476,477], and treatment of human subcutaneous adipose tissue explants with PRL also suppresses adiponectin release [475].
Read full chapter
URL: https://www.sciencedirect.com/science/article/pii/B9780123809261100057
Molecular and Cellular Endocrinology
Julian R.E. Davis, in Principles of Medical Biology, 1997
Summary
Prolactin is a polypeptide hormone produced by lactotropic cells in the anterior pituitary gland, and also a lower level by endometrial and lymphoid cells. It has effects on lactation, gonadal function, immune function, behavior, and osmoregulation. Prolactin receptors are members of the superfamily of cytokine receptors, and are linked to a cascade of protein kinases. Pituitary prolactin secretion is under tonic inhibitory control by hypothalamic dopamine, but is also regulated by a wide range of other factors.
The human prolactin gene contains two separate promoter regions and transcriptional start sites. Synthesis of prolactin in pituitary lactotropes depends on the presence of the transcription factor, Pit-1, which is also involved in mediating hormonal regulation through binding to the “pituitary” promoter. Extra-pituitary transcription of the human prolactin gene is independent of Pit-1, and depends on a separate upstream promoter adjacent to a noncoding “exon 1a.”
Pituitary prolactinomas are common, but their pathogenesis remains obscure. Their treatment commonly involves the dopaminergic D2-receptor agonist drug bromocriptine, which suppresses prolactin production but also induces tumor shrinkage.
Read full chapter
URL: https://www.sciencedirect.com/science/article/pii/S156925829780164X
Prolactin
Nadine Binart, in The Pituitary (Fourth Edition), 2022
Introduction
Prolactin (PRL) is mainly produced by pituitary lactotrophs and is tonically inhibited by the hypothalamus by the neurotransmitter dopamine. The discovery of multiple extrapituitary sites of PRL secretion also increases the range of known functions of this hormone. Its primary function is to enable breast milk production, although PRL receptors (PRLRs) are found in many other tissues.
The major isoform, 23-kDa PRL, acts via a membrane receptor, the prolactin receptor (PRLR), a thành viên of the hematopoietic cytokine superfamily, and for which the mechanism of activation has been elucidated. High levels of PRL in humans may interfere with reproductive function mainly by actions the hypothalamus.
Read full chapter
URL: https://www.sciencedirect.com/science/article/pii/B9780128041697000052
What is the function of prolactin in females quizlet?
The main role of prolactin in women is the regulation of milk production. Thus, prolactin, along with other hormones, is responsible for the proliferation and differentiation of mammary tissue. During birth, prolactin levels spike initiating lactation.Which of the following observations provides the best evidence that acetyl CoA negatively regulates?
Which of the following observations provides the best evidence that acetyl-CoA negatively regulates pyruvate dehydrogenase activity? The rate of the pyruvate dehydrogenase-catalyzed reaction is slower in the presence of a higher concentration of acetyl-CoA. Tải thêm tài liệu liên quan đến nội dung bài viết Which of the following best explains the presence of prolactin in various vertebrate species?
Post a Comment