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Endocrine Modulation of Myometrial Response*
Published in Gabor Huszar, The Physiology and Biochemistry of the Uterus in Pregnancy and Labor, 2020
R. Kirk Riemer, James M. Roberts
Upon fertilization and implantation of an ovum in the uterus, the major site of E and P synthesis in women shifts from the ovary to the placenta. The levels of E (primarily estriol) and P in myometrium increase throughout the course of pregnancy until just prior to parturition, when in some species, P levels decline preciptiously (this probably does not occur in humans, see below) while E levels continue to rise. The high E levels during pregnancy promote uterine hypertrophy and maintenance of high levels of contractile proteins as well as increasing myometrial sensitivity to the neurohypophyseal hormone OT. However, the E-induced enhancement of spontaneous contractile activity is suppressed, apparently because the concentration of P in myometrium is also high.
Regulation of the Pituitary Gland by Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
Interactions between DA and AVP also occur at the NL. A double-labeling technique has shown that dopaminergic nerve endings containing dense core vesicles 60–100 nm in diameter and small clear vesicles are always found in close proximity to vasopressin neurosecretory endings, suggesting interactions between the two systems [19]. In cultures of isolated rat neurohypophysial tissues, DA and selected agonists increased the release of both AVP and OT, and this was blocked by DA receptor antagonists [20]. These data suggest that the dopaminergic control of neurohypophysial hormone secretion also occurs at the level of the posterior pituitary, independent of the hypothalamus.
Pregnancy-Related Proteins Detected by Their Biological Activities
Published in Gábor N. Than, Hans Bohn, Dénes G. Szabó, Advances in Pregnancy-Related Protein Research, 2020
Litocin, a novel neurohypophyseal hormone found to be present in the human hypothalamus and pituitary gland could also be identified in human placental tissue.49 Litocin is a nonapeptide with a disulfide bond between position 1 and 6. The biological activities of Litocin found thus far are (1) anti-diuretic action, (2) decreased plasma osmolarity, (3) decreased plasma sodium level, and (4) uterotonic action. The physiological role of this neurohypophyseal hormone in pregnancy and reproduction remains to be elucidated.
Oxytocin modulates steroidogenesis-associated genes and estradiol levels in the placenta
Published in Systems Biology in Reproductive Medicine, 2023
Sung-Min An, Min Jae Kim, Jea Sic Jeong, So Young Kim, Da Som Kim, Beum-Soo An, Seung Chul Kim
Oxytocin (OXT) is a neurohypophyseal hormone synthesized by the hypothalamus and several peripheral tissues such as the corpus luteum, gonad, uterus, and placenta (Soloff et al. 1977; Swann et al. 1984; Sugahara et al. 1985; Watson et al. 1999). OXT is secreted by magnocellular neurons and is stored in the posterior pituitary until it is released into the bloodstream (Thackare et al. 2006; Johnson 2018). The released OXT acts directly via axon terminals on OXT receptors (OXTRs) in the CNS (e.g., the nucleus accumbens) (Knobloch and Grinevich 2014). Activation of OXTRs triggers the coupling of Gaq/11 and phospholipase C (PLC), which catalyzes the hydrolysis of diacylglycerol (DAG), phosphatidylinositol-4, and 5-bisphosphate (PIP2) to inositol-1, 4, 5-trisphosphate (IP3). Subsequently, inositol triphosphate causes an increase in Ca2+ influx from both intracellular and extracellular stores, whereas DAG facilitates the activation of protein kinase type C, which phosphorylates target proteins (Koehbach et al. 2013).
An overview of lantibiotic biosynthetic machinery promiscuity and its impact on antimicrobial discovery
Published in Expert Opinion on Drug Discovery, 2020
Interestingly the ability of applying the PTM ability of lantibiotic biosynthetic proteins is not just limited to the creation of lantibiotic variants. It has been reported that cyclization of therapeutic peptides is a successful strategy to improve their stability and biological properties [77–79]. Previous studies have demonstrated increased stability, activity and bio-availability of thioether bridged angiotensin (1–7) [80] In a recent study conducted by Li et al. 2019, the NisBTC modification system was utilized to replace the disulfide bridge in the neurohypophysial hormone Vasopressin with a thioether bridge with the aim to increase the stability of vasopressin in vivo. Results identified NisBTC could successfully replace the disulfide bridge with a thioether bridge although at a relatively low efficiency [81]. Whether this leads to an increase in stability of the vasopressin also needs further investigation. This study does however highlight how the promiscuous nature of the lantibiotic biosynthetic genes does not have to be restricted to lantiboitics and could help improve the pharmacological properties of a variety of clinical peptides currently in use.
Potential mechanism of thymosin-α1-membrane interactions leading to pleiotropy: experimental evidence and hypotheses
Published in Expert Opinion on Biological Therapy, 2018
Walter Mandaliti, Ridvan Nepravishta, Francesca Pica, Paola Sinibaldi Vallebona, Enrico Garaci, Maurizio Paci
Different examples have been reported such as oxytocin [59] and neurohypophyseal hormone-like peptides [60]. In the cases, it was proven that interaction with membranes was a method whereby peptides find receptors as in case of ghrelin [61], neuropeptide PPY-3 [62], or an analog of kyotorphin [63], for which interaction with membranes to reach the hERG potassium channel was studied [64], and apelin [65]. In some cases, the interaction was stepwise [66]; in other cases, the interaction with membranes was considered as a step of the action at the molecular level in cases such as the HIV inhibitor enfuvirtide [67] and the inhibitor Peptide T-1249, revealing a correlation with improved efficiency [68]. In other cases, improved efficacy can be attributed to interaction with the membrane [69,70] by a reduced molecular diffusion that can contribute to their kinetics of action just increasing the permanence of drug in time and, then, the duration of pharmacokinetic/pharmacodynamic effects [71,72]. This particular mode of action of peptides has been recently reviewed [72,73] with regard to the role of receptor(s) activation(s) upon binding to biological membranes [74]. In particular, the role (and the differences) of lipids involved in model membranes and in cell membranes has been studied [75]. This validates the idea that Tα1 can undergo a direct interaction with membranes in negative regions, namely exposed PS due to cell phospholipid unbalance, and that, after assuming partial structural elements, can be considered a model for the scheme of activity mechanism of Tα1 as an activator of biological cascade(s) upon interaction with different receptors. It is important to remark that this can be the basis of the observed pleiotropy of Tα1.