Oxytocin Receptors



Searching Google for "oxytocin receptors" yielded 766,000 references.   
oxytocin receptors - Google Search   
https://www.google.com/search?q=oxytocin+receptors&ie=utf-8&oe=utf-8&aq=t&rls=org.mozilla:en-US:official&client=firefox-a&channel=np&source=hp    


Oxytocin receptor (Wiki) 
http://en.wikipedia.org/wiki/Oxytocin_receptor    
    "The oxytocin receptor, also known as OXTR, is a protein which functions as receptor for the hormone and neurotransmitter oxytocin . [1] [2] "  
    "The OXTR protein belongs to the 
G-Protein Coupled Receptor  family, specifically Gq, [1]"  
    "Oxytocin receptors are also present in the central nervous system . These receptors modulate a variety of behaviors, including stress and anxiety, social memory and recognition, sexual and aggressive behaviors, bonding (affiliation) and maternal behavior. [9] [10] [11] "
My comments:         
1.  See the oxytocin article for more details.   
2. 
I looked at  Gq Proteins .   I'm not sure, but it looks like receipt of Oxytocin  by the
Gq Protein of an  Oxytocin Receptor  which is on a neuron would stimulate that neuron to release its neurotransmitter into the synaptic cleft at the end of its axon.  
Gq Proteins  serve other functions as well.  Click on the link to see them.  It's pretty complex and involves calcium ions.  
  

2001   
The oxytocin receptor system: structure, function, and regulation  (Goog)   -
    Free full text. 
Abstract 
http://www.ncbi.nlm.nih.gov/pubmed/11274341        
    "The neurohypophysial peptide oxytocin (OT) and OT-like hormones facilitate reproduction in all vertebrates at several levels.  
    The major site of OT gene expression is the magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei. In response to a variety of stimuli such as suckling, parturition, or certain kinds of stress, the processed OT peptide is released from the posterior pituitary into the systemic circulation. Such stimuli also lead to an intranuclear release of OT.  
    Moreover, oxytocinergic neurons display widespread projections throughout the central nervous system. However, OT is also synthesized in peripheral tissues, e.g., uterus, placenta, amnion, corpus luteum, testis, and heart.  
    The OT receptor is a typical class I G protein-coupled receptor that is primarily coupled via G(q) proteins to phospholipase C-beta. The high-affinity receptor state requires both Mg(2+) and cholesterol, which probably function as allosteric modulators."  
    "The function and physiological regulation of the OT system is strongly steroid dependent."  
    "OT also plays an important role in many other reproduction-related functions, such as control of the estrous cycle length, follicle luteinization in the ovary, and ovarian steroidogenesis. In the male, OT is a potent stimulator of spontaneous erections in rats and is involved in ejaculation.  
    OT receptors have also been identified in other tissues, including the kidney, heart, thymus, pancreas, and adipocytes. For example, in the rat, OT is a cardiovascular hormone acting in concert with atrial natriuretic peptide to induce natriuresis and kaliuresis. The central actions of OT range from the modulation of the neuroendocrine reflexes to the establishment of complex social and bonding behaviors related to the reproduction and care of the offspring. OT exerts potent antistress effects that may facilitate pair bonds. Overall, the regulation by gonadal and adrenal steroids is one of the most remarkable features of the OT system"  

The Oxytocin Receptor System: Structure, Function, and Regulation

    http://physrev.physiology.org/content/81/2/629.long    
Note:  This is a very long article with many references.  Although I've quoted only those sections I found most pertinent to my inquiry into the relationship between  Oxytocin and  Sociopathy , I've included all the headings to emphasize the breadth of the article. 


I. INTRODUCTION 

   "OT is a very abundant neuropeptide. This became obvious in a study where the most prevalent hypothalamic-specific mRNAs were analyzed. OT was found to be the most abundant of 43 transcripts identified ( 202 )."  
    "Over the past decade, particularly the central actions of OT have been intensively studied revealing a profound regulation by steroids."  


II. OXYTOCIN AND OXYTOCIN-LIKE PEPTIDES

A. Evolutionary Aspects    

    "All neurohypophysial hormones are nonapeptides with a disulfide bridge between Cys residues 1 and 6. This results in a peptide constituted of a six-amino acid cyclic part and a COOH-terminal alpha-amidated three-residue tail. Based on the amino acid at position 8, these peptides are classified into vasopressin and OT families: the vasopressin family contains a basic amino acid (Lys, Arg), and the OT family contains a neutral amino acid at this position (Table 1 ). Isoleucine in position 3 is essential for stimulating OT receptors and Arg or Lys in position 8 for acting on vasopressin receptors. The difference in the polarity of these amino acid residues is believed to enable the vasopressin and OT peptides to interact with the respective receptors (42)."  


Table 1.

Oxytocin and related peptides


    "The earthworm Eisenia foetida is the most primitive species from which an OT-related peptide (annetocin) has been isolated ( 429 ). Injection of annetocin in the earthworm or in leechs results in induction of egg-laying behavior ( 430 ). "  

My comment
    The above shows that oxytocin evolved before the split between the Protostomes   and the Deuterostomes .  What's more, it suggests that the original function of oxytocin-vasopressin was reproductive rather than water-balance.  If so, then the water-balance function of human vasopression evolved after the reproductive function of human oxytocin.  Further, it also suggests that the water-balance function only evolved when the lamprey swam inland to spawn and needed to adjust to the change in osmotic pressure from a salt water environment to a fresh water environment.   

B. Gene Structure    

"The OT prepropeptide is subject to cleavage and other modifications as it is transported down the axon to terminals located in the posterior pituitary ( 74 ). The mature peptide products, OT and its carrier molecule neurophysin, are stored in the axon terminals until neural inputs elicit their release ( 475 ). The main function of neurophysin, a small (93–95 residues) disulfide-rich protein, appears to be related to the proper targeting, packaging, and storage of OT within the granula before release into the bloodstream."  


III. OXYTOCIN RECEPTORS

A. Gene Structure and Regulation    

    "Kimura et al. ( 299 ) first isolated and identified a cDNA encoding the human OT receptor using an expression cloning strategy. The encoded receptor is a 389-amino acid polypeptide with 7 transmembrane domains and belongs to the class I G protein-coupled receptor (GPCR) family."  
    "The transcriptional regulation of OT receptor shows species-specific differences. The brain OT receptor varies across species in its distribution as well as in its regional regulation by gonadal steroids ( 261 , 262)."   

B. Receptor Structure    

    "The OT receptor is a typical member of the rhodopsin-type (class I) GPCR family. The seven transmembrane alpha-helices are most highly conserved among the GPCR family members."  

C. Ligand Binding Characteristics    

    "For small molecules like catecholamines, the ligands bind in a cavity between the alpha-helical segments formed by transmembrane domains 3–6. Peptide ligands, on the other side, bind more superficially and also interact with extracellular loops and/or the NH2-terminal domain. For the binding of the peptides OT and arginine vasopressin (AVP), residues located in the transmembrane domains as well as residues within extracellular domains are involved in ligand binding."  

D. Signal Transduction and G Protein Coupling

E. Receptor Internalization and Downregulation

F. Effects of Steroids
    1. Cholesterol
    2. Progesterone


IV. THE PERIPHERAL OXYTOCIN SYSTEM

A. Female Reproductive System
     1. Uterus
     2. Ovary and corpus luteum

B. Male Reproductive Tract
     1. Testis
     2. Prostate gland

C. Mammary Tissues
     1. Milk ejection
     2. Breast cancer and tumor cells

D. Kidney

E. Heart and Cardiovascular System

F. Other Localizations
     1. Thymus
     2. Fat cells
     3. Pancreas
     4. Adrenal gland

"Both solubilized and membrane-associated OT receptors require at least two essential components for high-affinity OT binding: divalent cations such as Mn2+ or Mg2+ and cholesterol. Compared with many other GPCRs, the GTP sensitivity of the agonist binding to the OT receptor is rather modest."  
    "Immunohistochemical studies in adrenal glands from rat, cow, hamster, and guinea pig showed that OT was localized in both the cortex and medulla in all these species."  
    "In the CNS, the OT gene is primarily expressed in magnocellular neurons in the hypothalamic PVN and SON. Action potentials in these neurosecretory cells trigger the release of OT from their axon terminals in the neurohypophysis ( 464 ). In the PVN, two populations of OT-staining neurons have been identified: magnocellular neurons that terminate in the neurohypophysis and parvocellular neurons that terminate elsewhere in the CNS. Only a small fraction (0.2%) of the OT neurons were calculated to possess axon collaterals to both the neurohypophysis and the extrahypothalamic areas.
    Although few OT perikarya were observed other than in the magnocellular nuclei, OT fibers and endings have been described in various brain areas in the rat: the dorsomedial hypothalamic nucleus, several thalamic nuclei, the dorsal and ventral hippocampus, subiculum, entorhinal cortex, medial and lateral septal nuclei, amygdala, olfactory bulbs, mesencephalic central gray nucleus, substantia nigra, locus coeruleus, raphe nucleus, the nucleus of the solitary tract, and the dorsal motor nucleus of the vagus nerve.  
    OT fibers also run toward the pineal gland and the cerebellum, with most of them continuing toward the spinal cord. A few OT fibers end on the portal capillaries in the median eminence (see references in Refs. 78 , 309 , 476 , 501 , 524 ). "  


V. THE CENTRAL OXYTOCIN SYSTEM

A. Localization Profile
    1. Localization of OT
        In the CNS, the OT gene is primarily expressed in magnocellular neurons in the hypothalamic PVN and SON. Action potentials in these neurosecretory cells trigger the release of OT from their axon terminals in the neurohypophysis ( 464 ). In the PVN, two populations of OT-staining neurons have been identified: magnocellular neurons that terminate in the neurohypophysis and parvocellular neurons that terminate elsewhere in the CNS. Only a small fraction (0.2%) of the OT neurons were calculated to possess axon collaterals to both the neurohypophysis and the extrahypothalamic areas.
    Although few OT perikarya were observed other than in the magnocellular nuclei, OT fibers and endings have been described in various brain areas in the rat:  
    the dorsomedial hypothalamic nucleus, several thalamic nuclei, the dorsal and ventral hippocampus, subiculum, entorhinal cortex, medial and lateral septal nuclei, amygdala, olfactory bulbs, mesencephalic central gray nucleus, substantia nigra, locus coeruleus, raphe nucleus, the nucleus of the solitary tract, and the dorsal motor nucleus of the vagus nerve. OT fibers also run toward the pineal gland and the cerebellum, with most of them continuing toward the spinal cord. A few OT fibers end on the portal capillaries in the median eminence (see references in Refs. 78 , 309 , 476 , 501 , 524 ).

OT concentrations in the extracellular fluid of the SON were calculated to be >100- to 1,000-fold higher than the basal OT concentration in plasma, i.e., more than 1–10 nM. High-frequency electrical discharges of OT neurons as they occur, e.g., during the milk ejection reflex, might release even higher local OT concentrations ( 321 ).

Plasma OT does not readily cross the blood-brain barrier, and there is no relationship between the release of OT into the blood by the neurohypophysis and the variations in OT concentrations in the cerebrospinal fluid (CSF). Peripheral stimulations such as suckling or vaginal dilation that elicit large increases in plasma OT may or may not change the concentration of OT in the CSF. As shown in rats, electrical stimulation of the neurohypophysis only evokes the release of OT into the blood, whereas stimulation of the PVN elicits a release of OT into the blood and into the CSF ( 228 ). After hypophysectomy, OT disappears from the blood, whereas its concentration increases in the CSF ( 139 ). The OT in the CSF is probably derived from neurons that extend to the third ventricle, the limbic system, the brain stem, and the spinal cord. In the CSF, OT is normally present at concentrations of 10–50 pM, and its half-life is much longer (28 min) than in the blood (1–2 min) ( 283 , 384 ). In humans and in monkeys, a circadian rhythm in the OT concentrations in the CSF has been found with peak values at midday. No such circadian rhythms have been observed in the CSF of rats, cats, guinea pigs, or goats. Circadian rhythms have never been observed in plasma OT concentrations ( 12 ).

Further complicating factors are the presence of an OT-like peptide and the appearance of conversion products of OT that possibly exert their effects exclusively on the brain, e.g., to influence learning and memory processes. Moreover, OT fragments such as OT-(1—6) or OT-(7—9) could cross the blood-brain barrier more easily ( 132 ).

    2. Localization of OT receptors

Experiments with primary cell cultures showed that OT receptors are localized both on hypothalamic neurons and astrocytes ( 136 ). Concerning the regional distribution of OT binding sites in the brain, marked species differences have been observed.  
    In rats, OT receptors are abundantly present in several brain regions, i.e., some cortical areas, the olfactory system, the basal ganglia, the limbic system, the thalamus, the hypothalamus, the brain stem, and the spinal cord (see Table 4 ). In the adult rat, a high density of OT receptors is found in the dorsal peduncular cortex, the anterior olfactory nucleus, the islands of Calleja and ventral pallidum cell groups, the limbic system (bed nucleus of the stria terminalis, central amygdaloid nucleus, ventral subiculum), and the hypothalamic ventromedial nucleus ( 43 , 561 ).  
    OT receptor mRNA was detected in brain areas mostly coinciding with the occurrence of OT binding sites ( 610 ). OT receptors were detectable in all spinal segments, but in low amounts and restricted to the superficial layers of the dorsal horn ( 557 ). No major differences in receptor distribution were observed between male and female brains. Notably, the distribution pattern of OT binding sites is markedly different from that of binding sites for AVP. Whenever present in the same area, OT and AVP binding sites were located in different parts of the area. View this table: Table 4.

Distribution of oxytocin receptors in the central nervous system

The distribution and numbers of OT binding sites undergo major changes during development. As shown by Tribollet et al. ( 561 ), only a fraction of OT receptors is constantly present during the development. Some OT receptors are only transiently expressed on neurons, e.g., during infancy or during maturation (Table 4 ). In male and in female rats, two critical periods during the development were recognized: the third postnatal week, which precedes weaning, and puberty. For example, in the infant brain, the cingulate and retrosplenial cortex as well as the substantia gelatinosa of the spinal cord contained the highest densities of OT binding sites, whereas low or undetectable numbers of OT receptors were observed in these areas in the adult rat brain. Conversely, OT receptors in some other areas were abundant in the adult brain but undetectable before puberty, e.g., in the olfactory tubercle (Calleja islands and ventral pallidum cell groups) and in the hypothalamic ventromedial nucleus ( 561 ) (Table 4 ). During aging, however, the number of OT binding sites decreased again in the latter areas. This was probably mediated by the markedly lower level of plasma testosterone in aged rats. In fact, the expression of OT receptors in the olfactory tubercle and in the ventromedial hypothalamic nucleus was shown to be dependent on gonadal steroids, and testosterone treatment of aging rats could restore normal adult levels of OT receptors in these areas ( 35 ).

As already mentioned, there is a high diversity of OT receptor distribution between different species. For example, the ventral subiculum in the hippocampus contains high densities of OT binding sites in the rat, whereas in the guinea pig, the hamster, the rabbit, and the marmorset, no OT binding sites were detected in this area. In the rabbit, no OT receptors were found in the hypothalamic ventromedial nucleus. In monogamous versus polygamous voles, OT receptor distribution was shown to reflect social organization ( 258 ). In human brains, dense OT receptor binding sites were visualized in the pars compacta of the substantia nigra unlike in several other species examined so far. Thus, in humans, nigrostriatal dopamine neurons could be a target for OT, and the OT system may be involved in motor and other basal ganglia-related functions. Strong OT binding intensity was also observed in the basal nucleus of Meynert, but OT binding sites were lacking in the hippocampus, amygdala, entorhinal cortex, and olfactory bulb of human brains ( 346 ) (Table 4 ).

In a few brain areas such as the ventral hippocampus and the bed nucleus of the stria terminalis (BNST), the reactivity of neurons to OT could be related with OT axon endings and OT receptors. The distribution of OT binding sites in the rat spinal cord was shown to coincide with that of the OT innervation, suggesting that OT is involved in sensory and autonomic functions ( 474 ). In most other brain areas, it was not possible to identify a clear relationship between the presence of the whole OT system and the physiological data. So, in male rats, Hosono et al. ( 244 ) identified a functional OT receptor system in the subfornical organ, where in binding studies the expression is almost neglected. Marked receptor-peptide mismatches exist in some brain regions, for example, in the amygdala, where very few OT afferents but highest OT binding activities have been found. On the other hand, one has to recognize that OT binding sites in regions with high OT concentrations may be downregulated to a level that may not be detectable by autoradiography using radioligands. In the lactating rat, for instance, OT binding sites have been found to be nearly undetectable in den PVN and SON. As soon as 5–20 min after intracerebroventricular injection of an OT antagonist, a strong increase of OT binding sites was noticed in the magnocellular nuclei. In this case, the presence of the OT antagonist may prevent the downregulation of OT receptors induced by the high concentrations of OT that are released into the magnocellular nuclei during lactation ( 183 ).

In the brain, estrogen has only a modest influence on the synthesis of OT, but it has a pronounced effect on the regulation of the OT receptor. OT receptors (but not AVP receptors) are regulated by gonadal steroids in the rat brain in a complex fashion ( 368 , 556 ). Castration and inhibition of aromatase activity reduced, whereas estradiol and testosterone increased OT binding, particularly in regions of the brain assumed to be involved in reproductive functions, such as the ventrolateral part of the hypothalamic ventromedial nucleus (VMN) and the islands of Calleja and neighboring cell groups ( 556 ). Estrogen treatment increased the affinity of OT receptors in the medial preoptic area-anterior hypothalamus ( 88 ) and increased both the density and the area of OT binding in the rat VMN ( 114 ). Progesterone caused a further increase in receptor binding and was required for a maximal extension of the area covered by OT receptors ( 114 , 509 ). In another study, chronic progesterone treatment increased basal OT receptor density in the limbic structures, decreased it in the ventromedial nucleus, and prevented estrogen-induced increases in ligand binding in all areas studied with the exception of the medial preoptic area ( 439 ). Glucocorticoids ( 340 ) have also been reported to modulate cerebral OT receptors ( 439 , 509 ). The brain OT receptor varies across species (compare rat versus human in Table 4 ) not only in its distribution but also in its regional regulation by gonadal steroids. For example, estrogen increased OT receptor binding in the rat brain but reduced OT receptor binding in the homologous regions of the mouse brain ( 262 ).

B. Hypothalamus-Neurohypophysis

The magnocellular neurons also release OT and VP from their perikarya, dendrites, and/or axon collaterals ( 335 , 467 ). Although the amount of release is small compared with the amount released from the neurohypophysis, the concentration of OT and VP in the extracellular fluid of the SON resulting from this somatodendritic release has been calculated to be 100- to 1,000-fold higher than the basal plasma concentration ( 319 ). Intranuclear release of these peptides occurs in response to a wide variety of stimuli, including suckling; parturation; hemorrhage; certain kinds of stress such as fever, physical restraint, and pain; mating and territorial marking behaviors; dehydration; administration of hypertonic solutions; and a range of pharmacological stimuli ( 318 , 349 , 476 ). The magnocellular neurons display characteristic activity patterns that are associated with particular secretion patterns for the peptide ( 475 ). For example, OT neurons respond to such stimuli as hyperosmolarity with small increases in spontaneous firing rate, whereas during lactation the same cells display explosive synchronized bursts of activity associated with a pulsatile release of OT into the circulation to cause contraction of mammary smooth muscle and milk let-down ( 475 ). PVN neurons can be identified as either AVP or OT secreting on the basis of their spontaneous discharge patterns. Interestingly, in most cases, central release patterns of OT are accompanied by peripheral ones, whereas release of AVP is not. In the rat, OT is released into the plasma without AVP, e.g., by suckling, parturition, stress, and nausea ( 603 ).

OT is required for successfull milk ejection in response to suckling as confirmed by the phenotype of OT knock-out mice (see sect.iv C). All offspring of these mice died shortly after birth because of the dam's inability to nurse. Postpartum injections of OT to the OT-deficient mothers restored milk ejection and rescued the offspring ( 416 ). OT released into the SON probably plays an essential role in the milk-ejection reflex, facilitating suckling-induced electrical activation of OT neurons ( 395 ). So, the injection of an OT antagonist into the SON prevented the OT-induced facilitation and completely interrupted the milk-ejection reflex ( 317 ). During parturition and suckling, OT is released within the SON ( 394 , 408 ) and apparently excites via a short positive-feedback loop the same cells by which it is produced and secreted ( 406 , 407 ). This autoexcitatory mechanism leads to further amplification of local and/or neurohypophysial OT release and ensures the synchrony of firing activity among oxytocinergic neurons. The underlying molecular mechanism of this putative autoexcitation is unclear. It was suggested that OT depresses the synaptic GABAergic input from perinuclear interneurons projecting into the SON ( 77 ). In addition to the magnocellular nuclei, the BNST may participate in the control of neuroendocrine responses during lactation ( 250 ). Injection of OT into the BNST increases the frequency of milk ejections, and electrophysiological recordings showed increased activity of BNST neurons coincident with this facilitatory effect ( 316 ).

All the physiological situations during which large amounts of OT are released into the blood are characterized by ultrastructural changes in the magnocellular nuclei, e.g., reduced astrocytic coverage of oxytocinergic somata and dendrites, increases in GABAergic synapses, increases in the juxtaposition of the membranes of the perikarya and of the dendrites between adjacents neurons, and increases in the contact area between neurosecretory terminals and the perivascular space. These morphological changes are reversible with cessation of stimulation, affect exclusively oxytocinergic neurons, and may serve to facilitate and maintain the characteristic synchronized electrical activity of these neurons at milk ejection ( 552 , 553 ). Neuronal network rearrangement may also occur after behavioral experience. So, in maternally experienced ewes, parturition-induced increases in the expression of OT receptor mRNA in the PVN and the islands of Calleja were potentiated ( 69 ).


C. Adenohypophysis

It has been suggested that some hypothalamic OT reaches the anterior pituitary lobe via the hypothalamo-pituitary portal vasculature. OT might thus be able to influence anterior pituitary hormones as a hypothalamic regulating factor. OT is present in nerve terminals in the median eminence. It was found to be released into the portal vessels, and specific OT receptors are present in the rat adenohypopophysis ( 18 , 494 ). Another pathway for OT delivery to the adenohypophysis might be the short portal vessels connecting the posterior and anterior lobes. OT may participate in the physiological regulation of the adenohypophysial hormones prolactin ( 433 ), ACTH ( 332 ), and the gonadotropins ( 484 ).

There was a long controversy on whether OT released in response to suckling was responsible for the concomitant secretion of prolactin from the adenohypophysis. During suckling and under stress, both hormones are quantitatively predominant among the factors released. OT could only act as prolactin releasing factor when the dopamine levels are low, e.g., during the brief periods of dopamine withdrawal that characterize the onset of prolactin secretion under various physiological stimuli ( 494 ). With the use of a cell-specific targeting approach, it was shown that a subpopulation of lactotrophs respond to OT ( 493 ). Breton et al. ( 68 ) demonstrated that the pituitary OT receptor gene expression is restricted to lactotrophs and dramatically increases at the end of gestation or after estrogen treatment. These findings question a direct function of OT on pituitary cells other than lactotrophs and suggest that OT might exert its full potential as a physiological prolactin-releasing factor only toward the end of gestation ( 68 ).

The major endocrine response to stress is via activation of the hypothalamic-pituitary-adrenal axis. ACTH secretion from the anterior pituitary is primarily regulated by CRH and AVP synthesized in neurons of the PVN. Unlike ACTH, plasma OT does not increase in response to all kinds of stress. In rats, OT can potentiate the release of ACTH induced by CRH. OT was also reported to stimulate ACTH secretion from corticotrophs in fetal and adult sheep ( 363 ). CRH is responsible for the immediate secretion of ACTH in response to stress. However, when the CRH levels are decreased following prolonged stress, the persistent level of OT in the median eminence could become important for the delayed ACTH response and for the generation of pulsatile ACTH secretory bursts ( 65 ).

In contrast, OT infusion into human volunteers actually inhibited the plasma ACTH responses to CRH ( 433 ). Suckling and breast stimulation in humans produced an increase in plasma OT and a decrease in plasma ACTH level. The observed negative correlation of both hormones indicates an inhibitory influence of OT on ACTH/cortisol secretion under a certain physiological condition in humans ( 11 , 107 ). Conclusively, OT might control ACTH release under some physiological conditions in a species-specific manner.

Gonadotropes in the adenohypophysis synthesize and secrete the two gonadotropin hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Although gonadotropin-releasing hormone (GnRH) is believed to be the primary secretagogue for LH, OT has also been shown to stimulate LH release. OT administered to proestrous rats caused advancement of the LH surge and earlier ovulation. In addition, OT antagonists inhibited the peak of LH at proestrous ( 484 ). On the other hand, OT receptors have not been detected on gonadotropes but were identified on a gonadotrope-derived cell line ( 162 ). Indirect effects of OT on LH release have also been discussed ( 160 ). OT has been observed to synergistically enhance GnRH-stimulated LH release. OT may sensitize the pituitary before full GnRH stimulation. In human females, preovulatory OT administration promoted the onset of the mid-cycle LH surge ( 248 ). Overall, the physiological connection between OT and LH release has yet to be definitively established ( 160 ).


D. Centrally Mediated Autonomic and Somatic Effects

    3. Motor activity

Centrally administered OT can induce or modify several forms of behavior together with the associated motor sequences. OT increased general motor activity, and OT antisera decreased this hyperactivity and seizures in a complementary fashion. In this context, OT may possibly act at the spinal level ( 59 ). OT changed the spontaneous motor activity in female rats in strong dependence on steroid hormones ( 444 ). Treatment with low OT doses led to a decrease in peripheral locomotor activity, whereas increasing doses of OT provoked sedative effects as indicated by a suppression of locomotor activity and rearing. A maximal effect was obtained within 1 h and thereafter, the behavior gradually returned to normal within 24 h ( 566 ). During static muscle contraction, blood pressure and heart rate reflexly increase as shown in anesthetized cats. In this respect, OT may participate to regulate cardiovascular responses elicited by contraction of skeletal muscle ( 338 , 476 ).


VI. CENTRAL BEHAVIORAL EFFECTS

A. Sexual Behavior

The “classical” peripheral target tissues for OT, uterus and mammary glands, are both organs linked to reproduction. There is also evidence that OT homologs in fish, amphibians, and reptiles as well as in molluscs and annelids are important in the control of reproductive behaviors. In the mollusc Lymnaea stagnalis, the conopressin gene encoding the putative ancestral receptor to the VP/OT receptor family is expressed in neurons that control male sexual behavior, and its gene products are present in the penis nerve and the vas deferens ( 569 ). Thus a phylogenetically old connection may exist between systems controlling reproductive hormone release and reproductive behaviors. Moreover, the neurohypophysial release of OT into the circulation is most efficiently provoked by various kinds of stimulations of genitals and the breast in different mammalian species ( 94 , 369 ).

Unlike humans, the majority of animals breed only during certain times of the year, and the expression of sexual behavior is under strict endocrine regulation. Male and female animals mate only when circulating steroid hormone levels are at appropriate concentrations, and to influence behavior, the steroid hormones must profoundly affect the neurotransmission in the brain. In contrast, humans and other primates display a phenomenon called “concealed ovulation” that may have played a role in the evolution of social structures ( 369 ).

    1. Female sexual behavior in animals  

View this table: Table 5.

Actions of oxytocin on behaviors in different species   

Other headings

    2. Male sexual behavior 

    3. Sexual behavior in humans 

B. Maternal Behavior 

C. Social Behavior 

D. Stress-Related Behavior 

E. Feeding and Grooming 

F. Memory and Learning 

G. Tolerance and Dependence to Opioids 

H. Central Disorders in Humans
    1. Obsessive-compulsive disorder 
    2. Eating disorders: anorexia and Prader-Willi syndrome 
     3. Depression and schizophrenia 
     4. Neurodegenerative diseases 


VII. CONCLUDING REMARKS

In the past decade, the OT receptor structure has been elucidated, and considerable advances have been made in understanding the structure and function of the OT receptor system that has now been detected in many different tissues. Is there a further OT receptor subtype as suggested by some findings? It is certainly too early to exclude this possibility. On the other hand, many of the unexplained observations in the OT receptor field may result from complex cross-talks to poorly defined signaling cascades, interactions with receptor modulators like Mg2+ and cholesterol, and/or regulation by steroids via genomic and nongenomic pathways. Particularly, the functional dependence on steroids, a characteristic feature of the OT receptor system, is among the least understood. This is not surprising in view of the multiple targets of steroids and the novel facets of steroid receptor actions. For example, recent observations suggest that several steroid receptors can be activated by various agents in the absence of cognate hormone ( 99 ). To clarify the underlying mechanisms for both genomic and nongenomic steroid actions will therefore be of fundamental importance to understand the physiological regulation of the OT receptor system.

To some extent, most of the different actions of OT can be integrated in a concept according to which OT supports and facilitates the reproduction at several levels. In social living species like humans, affiliative behaviors are an essential component of reproduction. It will be therefore interesting to see whether in humans, mislocations of the OT receptor, naturally occurring mutations, or polymorphisms in the OT receptor gene can be correlated with (gender-specific?) physiological or behavioral deficits. In view of the widespread OT-related actions, OT antagonists may not only be regarded as promising candidates to prevent preterm labor and dysmenorrhea, but may together with OT agonists also prove useful for treatment of psychiatric illnesses such as anxiety, drug abuse, sexual dysfunctions, eating disorders, or autism.
    "For more details to the different topics, the reader is referred to many excellent reviews that have been recently published ( 1 , 42 , 43 , 155 , 160 , 161 , 261 , 265 , 266 , 295 , 298 , 335 , 369 , 389 , 413 , 443 , 572 , 573 , 621 )."  

My comment
    Oxytocin has turned out to be much more complex than I anticipated.  I'm afraid that I'm going to be able to relate it to my mother's sociopathy in only the most general, phenominological way.     




Searching PubMed for "oxytocin receptors" yielded 4,526 references. 

oxytocin receptor - PubMed 
http://www.ncbi.nlm.nih.gov/pubmed/?term=oxytocin+receptor    







SubC: Oxytocin Receptors 
181014 - 1048  

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