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

The discovery of the various peptide factors in the gonads followed different paths. A number of factors were specifically searched for because of physiological experiments that predicted that an activity from the gonads was necessary to explain phenomena. Such was the case for gonadal steroids and for such peptide factors as inhibin, MIS, OMI, FRP, seminal plasma inhibin, relaxin, PA factor and other proteases, and ABP. In the process other factors such as activin and follistatin were serendipitously discovered. A second group of factors was discovered because in vitro experiments of various combinations of gonadal cell types failed to replicate in vivo findings, suggesting missing signals. Such substances are the panoply of growth factors aiding in differentiation and growth promotion and inhibition: LS and LI, P-Mod-S, clusterin, and various components of the ECM. Finally, and most recently, another set of peptides has been identified because immunological or molecular probes have been used to search gonadal tissue for factors originally discovered elsewhere; these include POMC, GnRH-like peptide, oxytocin, AVP, angiotensin, ANF, CRF, neural peptides, and c-mos. Our understanding of the relationship of most of these peptides to the local signals necessary for gonadal function is still very elementary. Clearly some like relaxin and inhibin function as important hormones, and ABP, for example, probably functions importantly in transporting testosterone down the tubule. Most local paracrine or autocrine peptide signals appear to act in relationship to gonadotropin levels probably in local differentiation in the process of gamete maturation, but this is only conjecture at this point. No experimental verification that any of these factors is involved in follicle selection for recruitment or for atresia is yet available. For many of the factors local receptors have not yet been identified. The richness of the variety of peptides in the gonads suggests that microanalysis of cell-cell signaling would be rewarding, but at the time of this writing such investigations are not yet possible.
 ...
PMID:Nonsteroidal signals originating in the gonads. 162 34

The time- and dose-dependent effects of bovine FSH-suppressing protein (FSP)/follistatin and human recombinant activin A (hr-Act) on oxytocin (OT) and progesterone (P) production, markers of luteinization, were studied in mature and immature bovine granulosa cells (GC), using three forms of FSP (31, 35, and 39 kDa) and a FSP pool consisting of 35, 39, and 45 kDa forms. FSP alone had no detectable effect on OT and P production when added to cultures of fully differentiated bovine GC. On the other hand, all FSP forms (10-100 ng/ml) enhanced and prolonged OT and P production of immature GC induced by bovine LH (10 ng/ml). Overall, 35 kDa FSP was more effective than the other forms tested. Hr-Act alone had a dose-dependent inhibitory effect on OT and P production on LH-stimulated immature GC. All four forms of FSP (30 or 100 ng/ml) added to cultures treated with hr-Act, reversed the inhibitory effect of hr-Act, with a significant increase (25%) above control levels using the 35 and 39 kDa FSP forms. In conclusion, FSP enhanced and prolonged the luteinization process, as indicated by OT and P production induced in immature GC by bovine LH, and was able to antagonize the inhibitory effect of hr-Act in this system. These studies suggest a physiological role for activin and FSP, as modulators of folliculogenesis and luteinization in the ovary. We propose that activin and FSP act in an autocrine fashion on GC in the ovarian follicle to regulate folliculogenesis and luteinization.
 ...
PMID:The effect of follicle-stimulating hormone-suppressing protein or follistatin on luteinizing bovine granulosa cells in vitro and its antagonistic effect on the action of activin. 195 13

We have previously demonstrated that neuronal oxytocin mRNA increases during the pubertal development of female rats. In this paper we have examined the factors that regulate this developmental increase in both male and female rats. Northern blot analysis demonstrated that neural oxytocin mRNA increased 5- to 10-fold from postnatal day 20 (P20) to P60 in animals of both sexes, coincident with puberty. Mature male rats and females at all stages of the estrous cycle expressed similar levels of neural oxytocin mRNA. Pubertal up-regulation of oxytocin mRNA was largely, but not completely, inhibited by prepubescent gonadectomy, indicating a requirement for intact gonads as well as some other as yet undefined factor(s). Pubertal treatment of gonadectomized animals with estradiol or testosterone abolished the effects of gonadectomy; treated animals expressed levels of neural oxytocin mRNA similar to those in controls. However, treatment of prepubertal animals with estradiol or testosterone from P10 to P20 had no effect on oxytocin mRNA levels, suggesting that neural maturation or other factors are necessary requisites for steroid sensitivity. To determine whether neural activin played any role in regulating oxytocin mRNA during puberty, we examined levels of inhibin/activin beta A-chain mRNA. This mRNA was expressed at similar levels in all brain regions and did not vary as a function of gonadectomy or steroid treatment, making it unlikely that activin mediates the observed changes. Together, these data indicate that neural oxytocin mRNA is induced by gonadal steroids during puberty, and suggest a mechanism for coordinating development of reproductive functions with other pubertal changes.
 ...
PMID:Regulation of neural oxytocin gene expression by gonadal steroids in pubertal rats. 208 96

The aim was to examine the effect of activin on luteinization of preovulatory bovine granulosa cells in vitro. Bovine activin-A was found to inhibit the production of oxytocin (OT) and progesterone by bovine granulosa cells from individual preovulatory follicles cultured in serum-free medium. The minimal response on OT production (25% inhibition) occurred with 0.1-1 ng/ml activin-A, and the maximal inhibition (83%) occurred with 10 ng/ml activin-A after 2-3 days in culture. Progesterone showed a similar response (30% inhibition for 0.1-1 ng/ml and 74% for 10 ng/ml). Inhibin production was not consistently effected by activin-A. Inhibin (75 U/ml) had no detectable effect upon OT or progesterone production. When activin-A was withdrawn from the cell culture after 72 h and the incubation continued for a further 72 h, a recovery in OT was seen on day 4 and 5 after activin-A doses of 0.1-1 ng/ml, but not after higher doses (3 and 10 ng/ml). Progesterone did not show a recovery, but the levels remained constant for 3 days (0.1 and 0.3 ng/ml activin-A) or for 1 day (1-10 ng/ml activin-A) and then fell to control levels by day 6 of culture. We conclude that bovine activin-A has an autocrine action on bovine granulosa cells in vitro, to inhibit basal production of OT and progesterone, consistent with the role of activin-A in delaying the process of luteinization.
 ...
PMID:Activin-A inhibits oxytocin and progesterone production by preovulatory bovine granulosa cells in vitro. 231 63

Follistatin (FS), which binds to the inhibin/activin beta A- or beta B-subunit is localized with and modulates the biological actions of activin in many systems. However, in contrast to the wide distribution of the activin beta-subunit proteins and messenger RNAs (mRNA) in the brain, demonstration of FS mRNA signal has been limited to the olfactory tubercle and layer II of the frontal cortex. We have hypothesized a more extensive distribution of central FS gene expression and localization in regions coinciding with inhibin/activin beta-subunits and possible activin-mediated effects. In the present study, we examined the central distribution of FS mRNA expression in the normal adult male rat. With in situ hybridization analysis, using a 33P-labeled RNA probe specific for rat FS, gene expression is shown to be widely distributed throughout the brain. Abundant FS mRNA expression is localized in several areas of the olfactory bulb as well as the frontal cortex, a few thalamic nuclei, and in septal regions. Moderate FS mRNA is observed in the caudate putamen and various hypothalamic areas including the paraventricular, ventromedial, dorsomedial, and arcuate nuclei. Several brain stem regions are also found to express FS mRNA, including the medial vestibular and solitary tract nuclei. Notably, FS mRNA, including the medial vestibular and solitary septal/diagonal band region is localized in patterns that are highly correlative with those of GnRH gene expression and hence may serve to regulate possible activin-mediated effects in these areas. FS mRNA is also expressed in areas associated with the activin-oxytocin pathway (solitary tract nucleus and paraventricular nucleus) and is therefore in a position to modulate the role of activin in the solitary tract nucleus-paraventricular nucleus pathway (afferent system mediating the milk-ejection reflex). The results suggest that FS is centrally localized in sites compatible with a role in the regulation of central reproductive functions.
 ...
PMID:Distribution of follistatin messenger ribonucleic acid in the rat brain: implications for a role in the regulation of central reproductive functions. 861 60

Peritubular myoid cells, surrounding the seminiferous tubules in the testis, have been found in all mammalian species, but their organization in the peritubular interstitial tissue varies by species. In laboratory rodents, including rats, hamsters and mice, only one layer of myoid cells is seen in the testis. The cells in these animals are joined by junctional complexes as are epithelial cells. On the other hand, several cellular layers exist in the lamina propria of the seminiferous tubule in the human and some other animals. Myoid cells contain abundant actin filaments which are distributed in the cells in a species-specific manner. In the rat, the filaments within one myoid cell run both longitudinally and circularly to the long axis of the seminiferous tubule, exhibiting a lattice-work pattern. The arrangement of the actin filaments in the cells changes during postnatal development, and the disruption of spermatogenesis, such as cryptorchidism, seems to affect further the arrangement of the filaments. Other cytoskeletal proteins, including myosin, desmin/vimentin and alpha-actinin, are also found in the cells. Myoid cells have been shown to be contractile, involved in the transport of spermatozoa and testicular fluid in the tubule. Several substances (prostaglandins, oxytocin, TGF beta, NO/cGMP) have been suggested to affect the contraction of the cell, though the mechanisms of the contraction are still unknown. Recent in vitro studies have demonstrated that the cells secrete a number of substances including extracellular matrix components (fibronectin, type I and IV collagens, proteoglycans) and growth factors (PModS, TGF beta, IGF-I, activin-A). Some of these substances are known to affect the Sertoli cell function. Furthermore, it has been reported that myoid cells contain androgen receptors and are involved in retinol processing. Considering all this, it is evident that peritubular myoid cells not only provide structural integrity to the tubule but also take part in the regulation of spermatogenesis and the testicular function. Their precise roles, however, remain to be solved.
 ...
PMID:Peritubular myoid cells in the testis: their structure and function. 872 59

Inhibin and activin are best known as gonadal glycoprotein hormones but have a broad anatomical distribution. We previously described the central distribution ofinhibin/activin beta A- and beta B-subunit proteins in some neuronal cell bodies, fibers, and nuclei of the rat brain and reported a possible role for central activin in suckling-induced oxytocin secretion and corticotropin releasing factor release. In the present report, we mapped the detailed immunohistochemical localization of inhibin/activin alpha-, beta A-, and beta B-subunits throughout the rat brain to further clarify their central distribution. In addition, the localization and distribution of their corresponding mRNAs was assessed. The results are summarized as follows: 1) Both beta A- and beta B-subunit immunoreactivity are found in neuronal cell bodies in the nucleus of the solitary tract and the dorsal and ventral medullary reticular nuclei, and in fibers and terminals of known projection sites for these nuclei. 2) beta B-subunit immunoreactivity is localized in a group of perifornical neurons in the hypothalamus. 3) beta A-subunit immunoreactivity is present in discrete populations of neuronal cell nuclei scattered throughout the CNS. 4) mRNAs encoding each of the inhibin/activin subunits are expressed in all major brain regions as determined by S1 nuclease assay and in a variety of specific neuroanatomical sites as shown by in situ hybridization. The results suggest that central inhibin and activin proteins are produced in the brain where they may potentially serve inter- and intracellular functions in multiple systems.
 ...
PMID:Hybridization histochemical and immunohistochemical localization of inhibin/activin subunits and messenger ribonucleic acids in the rat brain. 882 Aug 78

Activin A (beta A-beta A) and activin B (beta B-beta B) are related dimeric proteins that regulate numerous cellular activities. Activin activity is bioneutralized by follistatin, a specific and high-affinity binding protein. Recently, our group developed specific and sensitive enzyme-linked immunosorbent activin assays that do not detect either activin isoform when bound to follistatin, therefore, the assays are specific for biologically relevant ligands. Activin A is measurable in the serum of pregnant women (cross-sectional sample collection), while activin B is not detected in maternal serum. However, activin B is measurable in amniotic fluid and cord blood sera. The purpose of this study was to measure serum activin A, activin B, and follistatin prospectively in longitudinally collected samples during pregnancy. This study design offered observations of relative changes in serum hormone concentration with each person serving as an internal reference. Serum samples were collected bimonthly from seven pregnant women beginning within the second month of gestation, and up to, but not including, the onset of labor. Six of the seven women had normal labor and delivery. One patient required pitocin (an oxytocin agonist) for induction of labor which led to delivery. Activin A, activin B, total follistatin, free follistatin, human chorionic gonadotropin, estradiol, progesterone, FSH, and LH were measured in maternal serum samples using specific assays. Serum activin A levels increased in the final month of pregnancy in the six patients who delivered following normal labor (< 0.78 ng/ml (first trimester) to 1-6 ng/ml (term)). Activin B was not detected in any serum sample (< 0.78 pg/ml). Total serum follistatin (free follistatin, follistatin-activin, and follistatin-inhibin) increased 10- to 45-fold in the final month of pregnancy in four of the women undergoing normal labor (10 ng/ml (first trimester) to 100-450 ng/ml (final month)). Total follistatin was high and variable in two women throughout pregnancy. Total follistatin returned to basal serum concentration in three of the patients during the last 2 weeks of pregnancy. Free follistatin was detected throughout pregnancy (range < 2-35 ng/ml). Free follistatin represented a small percentage of the total follistatin throughout the time of pregnancy and did not rise coincident with the rise in total follistatin. Serum activin A and activin B were not detected during the entire course of pregnancy in the one patient who did not have normal labor and total follistatin did not rise in the last trimester of pregnancy. Gonadotropin and steroid hormones were measured in all patients and were within normative ranges for human pregnancy (inclusive of the non-laboring patient). The results suggest that immunodetectable activin A is present in the third trimester of pregnant women who have normal onset labor. The total follistatin assay results suggest that follistatin-activin (or -inhibin) complexes are upregulated during the third trimester of pregnancy. Importantly, activin A production exceeds the binding capacity of circulating follistatin. Because binding protein free activin A is biologically active we conclude that the activin A detected in late pregnancy is biologically relevant. The findings are consistent with our hypothesis that activin A is an endocrine factor during the last trimester of human pregnancy and may be involved in normal labor.
 ...
PMID:Activin A and follistatin are dynamically regulated during human pregnancy. 907 73

Gonadotropin secretion by the pituitary gland is under the control of luteinizing hormone-releasing hormone (LHRH) and the putative follicle-stimulating hormone-releasing factor (FSHRF). Lamprey III LHRH is a potent FSHRF in the rat and appears to be resident in the FSH controlling area of the rat hypothalamus. It is an analog of mammalian LHRH and may be the long-sought FSHRF. Gonadal steroids feedback at hypothalamic and pituitary levels to either inhibit or stimulate the release of LH and FSH, which is also affected by inhibin and activin secreted by the gonads. Important control is exercised by acetylcholine, norepinephrine (NE), dopamine, serotonin, melatonin and glutamic acid (GA). Furthermore, LH and FSH also act at the hypothalamic level to alter secretion of gonadotropins. More recently, growth factors have been shown to have an important role. Many peptides act to inhibit or increase release of LH, and the sign of their action is often reversed by estrogen. A number of cytokines act at the hypothalamic level to suppress acutely the release of LH but not FSH. NE, GA and oxytocin stimulate LHRH release by activation of neural nitric oxide synthase (nNOS). The pathway is as follows: oxytocin and/or GA activate NE neurons in the medial basal hypothalamus (MBH) that activate NOergic neurons by alpha1 receptors. The NO released diffuses into LHRH terminals and induces LHRH release by activation of guanylate cyclase (GC) and cyclooxygenase. NO not only controls release of LHRH bound for the pituitary, but also that which induces mating by actions in the brain stem. An exciting recent development has been the discovery of the adipocyte hormone, leptin, a cytokine related to tumor necrosis factor-alpha (TNF-alpha). In the male rat, leptin exhibits a high potency to stimulate FSH and LH release from hemipituitaries incubated in vitro, and increases the release of LHRH from MBH explants by stimulating the release of NO. LHRH and leptin release LH by activation of NOS in the gonadotropes. The NO released activates GC that releases cyclic GMP which induces LH release. Leptin induces LH release in conscious, ovariectomized estrogen-primed female rats, presumably by stimulating LHRH release. At the effective dose of estrogen to activate LH release, FSH release is inhibited. Leptin may play an important role in induction of puberty and control of LHRH release in the adult as well.
 ...
PMID:Hypothalamic control of FSH and LH by FSH-RF, LHRH, cytokines, leptin and nitric oxide. 973 Jun 86

Gonadotropin secretion by the pituitary gland is under the control of luteinizing hormone-releasing hormone (LHRH) and the putative follicle stimulating hormone-releasing factor (FSHRF). Lamprey III LHRH is a potent FSHRF in the rat and seems to be resident in the FSH controlling area of the rat hypothalamus. It is an analog of mammalian LHRH and may be the long sought FSHRF. Gonadal steroids feedback at hypothalamic and pituitary levels to either inhibit or stimulate the release of LH and FSH, which is also affected by inhibin and activin secreted by the gonads. Important control is exercised by acetylcholine, norepinephrine (NE), dopamine, serotonin, melatonin, and glutamic acid (GA). Furthermore, LH and FSH also act at the hypothalamic level to alter secretion of gonadotropins. More recently, growth factors have been shown to have an important role. Many peptides act to inhibit or increase release of LH and the sign of their action is often reversed by estrogen. A number of cytokines act at the hypothalamic level to suppress acutely the release of LH but not FSH. NE, GA, and oxytocin stimulate LHRH release by activation of neural nitric oxide synthase (nNOS). The pathway is as follows: oxytocin and/or GA activate NE neurons in the medial basal hypothalamus (MBH) that activate NOergic neurons by alpha, (alpha 1) receptors. The NO released diffuses into LHRH terminals and induces LHRH release by activation of guanylate cyclase (GC) and cyclooxygenase. NO not only controls release of LHRH bound for the pituitary, but also that which induces mating by actions in the brain stem. An exciting recent development has been the discovery of the adipocyte hormone, leptin, a cytokine related to tumor necrosis factor (TNF) alpha. In the male rat, leptin exhibits a high potency to stimulate FSH and LH release from hemipituitaries incubated in vitro, and increases the release of LHRH from MBH explants. LHRH and leptin release LH by activation of NOS in the gonadotropes. The NO released activates GC that releases cyclic GMP, which induces LH release. Leptin induces LH release in conscious, ovariectomized estrogen-primed female rats, presumably by stimulating LHRH release. At the effective dose of estrogen to activate LH release, FSH release is inhibited. Leptin may play an important role in induction of puberty and control of LHRH release in the adult as well.
 ...
PMID:Hypothalamic control of gonadotropin secretion by LHRH, FSHRF, NO, cytokines, and leptin. 978 37


1 2 Next >>