Activins and their receptors in female reproduction

2000 ◽  
Vol 78 (3) ◽  
pp. 261-279 ◽  
Author(s):  
Chun Peng ◽  
Spencer T Mukai
Keyword(s):  
Transforming Growth Factor ◽  
Hormone Secretion ◽  
Transforming Growth Factor Β ◽  
Gonadotropin Releasing Hormone ◽  
Receptor Expression ◽  
Type I ◽  
Female Reproduction ◽  
Hormone Production ◽  
Releasing Hormone ◽  
Reproductive Axis

Activins are growth and differentiation factors belonging to the transforming growth factor-β superfamily. They are dimeric proteins consisting of two inhibin β subunits. The structure of activins is highly conserved during vertebrate evolution. Activins signal through type I and type II receptor proteins, both of which are serine/threonine kinases. Subsequently, downstream signals such as Smad proteins are phosphorylated. Activins and their receptors are present in many tissues of mammals and lower vertebrates where they function as autocrine and (or) paracrine regulators of a variety of physiological processes, including reproduction. In the hypothalamus, activins are thought to stimulate the release of gonadotropin-releasing hormone. In the pituitary, activins increase follicle-stimulating hormone secretion and up-regulate gonadotropin-releasing hormone receptor expression. In the ovaries of vertebrates, activins are expressed predominantly in the follicular layer of the oocyte where they regulate processes such as folliculogenesis, steroid hormone production, and oocyte maturation. During pregnancy, activin-A is also involved in the regulation of placental functions. This review provides a brief overview of activins and their receptors, including their structures, expression, and functions in the female reproductive axis as well as in the placenta. Special effort is made to compare activins and their receptors in different vertebrates. Key words: activins, activin receptors, reproductive axis, placenta.

scholarly journals Integrin β1Signaling Is Necessary for Transforming Growth Factor-β Activation of p38MAPK and Epithelial Plasticity

2001 ◽  
Vol 276 (50) ◽  
pp. 46707-46713 ◽  
Author(s):  
Neil A. Bhowmick ◽  
Roy Zent ◽  
Mayshan Ghiassi ◽  
Maureen McDonnell ◽  
Harold L. Moses
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Transcriptional Activation ◽  
Intracellular Signaling ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Dominant Negative ◽  
Receptor Expression ◽  
Type I ◽  
Type Ii

Transforming growth factor-β (TGF-β) can induce epithelial to mesenchymal transdifferentiation (EMT) in mammary epithelial cells. TGF-β-meditated EMT involves the stimulation of a number of signaling pathways by the sequential binding of the type II and type I serine/threonine kinase receptors, respectively. Integrins comprise a family of heterodimeric extracellular matrix receptors that mediate cell adhesion and intracellular signaling, hence making them crucial for EMT progression. In light of substantial evidence indicating TGF-β regulation of various β1integrins and their extracellular matrix ligands, we examined the cross-talk between the TGF-β and integrin signal transduction pathways. Using an inducible system for the expression of a cytoplasmically truncated dominant negative TGF-β type II receptor, we blocked TGF-β-mediated growth inhibition, transcriptional activation, and EMT progression. Dominant negative TGF-β type II receptor expression inhibited TGF-β signaling to the SMAD and AKT pathways, but did not block TGF-β-mediated p38MAPK activation. Interestingly, blocking integrin β1function inhibited TGF-β-mediated p38MAPK activation and EMT progression. Limiting p38MAPK activity through the expression of a dominant negative-p38MAPK also blocked TGF-β-mediated EMT. In summary, TGF-β-mediated p38MAPK activation is dependent on functional integrin β1, and p38MAPK activity is required but is not sufficient to induce EMT.

scholarly journals Highly redundant neuropeptide volume co-transmission underlying episodic activation of the GnRH neuron dendron

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Xinhuai Liu ◽  
Shel-Hwa Yeo ◽  
H James McQuillan ◽  
Michel K Herde ◽  
Sabine Hessler ◽  
...  
Keyword(s):  
Functional Significance ◽  
Hormone Secretion ◽  
Gonadotropin Releasing Hormone ◽  
Receptor Expression ◽  
Gnrh Neuron ◽  
Neurokinin B ◽  
Releasing Hormone ◽  
Pulsatile Hormone Secretion ◽  
Kndy Neurons

The necessity and functional significance of neurotransmitter co-transmission remains unclear. The glutamatergic ‘KNDy’ neurons co-express kisspeptin, neurokinin B (NKB), and dynorphin and exhibit a highly stereotyped synchronized behavior that reads out to the gonadotropin-releasing hormone (GnRH) neuron dendrons to drive episodic hormone secretion. Using expansion microscopy, we show that KNDy neurons make abundant close, non-synaptic appositions with the GnRH neuron dendron. Electrophysiology and confocal GCaMP6 imaging demonstrated that, despite all three neuropeptides being released from KNDy terminals, only kisspeptin was able to activate the GnRH neuron dendron. Mice with a selective deletion of kisspeptin from KNDy neurons failed to exhibit pulsatile hormone secretion but maintained synchronized episodic KNDy neuron behavior that is thought to depend on recurrent NKB and dynorphin transmission. This indicates that KNDy neurons drive episodic hormone secretion through highly redundant neuropeptide co-transmission orchestrated by differential post-synaptic neuropeptide receptor expression at the GnRH neuron dendron and KNDy neuron.

Novel Biology of Tachykinins in Gonadotropin-Releasing Hormone Secretion

2019 ◽  
Vol 37 (03) ◽  
pp. 109-118 ◽  
Author(s):  
Silvia Leon ◽  
Víctor M. Navarro
Keyword(s):  
Hormone Secretion ◽  
Gonadotropin Releasing Hormone ◽  
Optimal Timing ◽  
Releasing Hormone ◽  
Open Questions ◽  
Reproductive Axis ◽  
Gnrh Release ◽  
Timing Of Puberty ◽  
Puberty Onset ◽  
Luteinizing Hormone Surge

AbstractThe tachykinin family of peptides, composed of the neurokinins A and B (NKA, NKB) and substance P are involved in the central control of gonadotropin-releasing hormone (GnRH) release through a variety of neuronal circuitries that mediate the activation of Kiss1 neurons and the synchronization of their activity within the arcuate nucleus. The major outcome of this role is the precise regulation of the pulsatile pattern of GnRH release. In addition, tachykinins are involved in the maturation of the reproductive axis by determining the optimal timing of puberty onset, as well as in the timing of the preovulatory luteinizing hormone surge in females. Therefore, the action of tachykinins in reproduction appears to extend to all the critical aspects required for the successful attainment and maintenance of fertility. In this review, we summarize the latest advances in our understanding of the biology of tachykinins in the control of GnRH release, addressing the existing controversies, open questions, and future perspectives.

scholarly journals Differential expression of mRNAs encoding the putative inhibin co-receptor (betaglycan) and activin type-I and type-II receptors in preovulatory and prehierarchical follicles of the laying hen ovary

2006 ◽  
Vol 188 (2) ◽  
pp. 241-249 ◽  
Author(s):  
T M Lovell ◽  
P G Knight ◽  
R T Gladwell
Keyword(s):  
Mrna Expression ◽  
Transforming Growth Factor ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Transforming Growth Factor Β ◽  
Receptor Expression ◽  
Type I ◽  
Follicle Development ◽  
Ovarian Follicle Development ◽  
Real Time Quantitative Pcr

Ovarian follicle development is primarily regulated by an interplay between the pituitary gonadotrophins, LH and FSH, and ovary-derived steroids. Increasing evidence implicates regulatory roles of transforming growth factor-β (TGFβ) superfamily members, including inhibins and activins. The aim of this study was to identify the expression of mRNAs encoding key receptors of the inhibin/activin system in ovarian follicles ranging from 4 mm in diameter to the dominant F1 follicle (~40 mm). Ovaries were collected (n=16) from mid-sequence hens maintained on a long-day photoschedule (16 h of light:8 h of darkness). All follicles removed were dissected into individual granulosa and thecal layers. RNA was extracted and cDNA synthesized. Real-time quantitative PCR was used to quantify the expression of mRNA encoding betaglycan, activin receptor (ActR) subtypes (type-I, -IIA and -IIB) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH); receptor expression data were normalized to GAPDH expression. Detectable levels of ActRI, -IIA and -IIB and the inhibin co-receptor (betaglycan) expression were found in all granulosa and thecal layers analysed. Granulosa ActRI mRNA peaked (P < 0.05) in 8–9.9 mm follicles, whereas ActRIIA rose significantly from 6–7.9 mm to 8–9.9 mm, before falling to F3/2; levels then rose sharply (3-fold) to F1 levels. Granulosa betaglycan mRNA expression rose 3-fold from 4–5.9 mm to 8–9.9 mm, before falling 4-fold to F3/2; levels then rose sharply (4-fold) to F1 levels. ActRIIB levels did not vary significantly during follicular development. Thecal ActRI mRNA expression was similar from 4–7.9 mm then decreased significantly to a nadir at the F4 position, before increasing 2-fold to the F1 (P < 0.05). Although thecal ActRIIB and -IIA expression did not vary significantly from 4 mm to F3, ActRIIB expression increased significantly (2-fold) from F3 to F1 and ActRIIA increased 2-fold from F2 to F1 (P < 0.05). Thecal betaglycan fell to a nadir at F6 after follicle selection; levels then increased significantly to F2, before falling ~50% in the F1. In all follicles studied expression of betaglycan and ActRI (granulosa: r=0.65, P < 0.001, n=144/group; theca: r=0.49, P < 0.001, n=144/group) was well correlated. No significant correlations were identified between betaglycan and ActRIIA or -IIB. Considering all follicles analysed, granulosa mRNA expression of betaglycan, ActRI, ActRIIA and ActRIIB were all significantly lower than in corresponding thecal tissue (betaglycan, 11.4-fold; ActRIIB, 5.1-fold; ActRI, 3.8-fold; ActRIIA, 2.8-fold). The co-localization of type-I and -II activin receptors and betaglycan on granulosa and thecal cells are consistent with a local auto/paracrine role of inhibins and activins in modulating ovarian follicle development, selection and progression in the domestic fowl.

The effect of inflammation on the synthesis of luteinizing hormone and gonadotropin-releasing hormone receptor expression in the pars tuberalis of ewe during different photoperiodic conditions

2018 ◽  
Vol 98 (4) ◽  
pp. 675-687 ◽  
Author(s):  
Karolina Wojtulewicz ◽  
Dorota Tomaszewska-Zaremba ◽  
Agata Krawczyńska ◽  
Monika Tomczyk ◽  
Andrzej Przemysław Herman
Keyword(s):  
Gene Expression ◽  
Luteinizing Hormone ◽  
Follicular Phase ◽  
Gnrh Receptor ◽  
Gonadotropin Releasing Hormone ◽  
Receptor Expression ◽  
Pars Tuberalis ◽  
Type I ◽  
Releasing Hormone ◽  
Gene And Protein Expression

The study was designed to determine the effect of endotoxin-induced inflammation on luteinizing hormone (LH) synthesis and gonadotropin-releasing hormone (GnRH) receptor expression in the pars tuberalis (PT) of ewes during anestrous season and follicular phase taking into account the time of the day. Moreover, the effect of inflammation on the release of melatonin and its type I receptor gene expression in the PT was also determined. Lipopolysaccharide administration reduced nocturnal release of melatonin only during anestrous season, but it did not influence the gene expression of melatonin type I receptor in the PT. Inflammation inhibited nocturnal increase in the gene and protein expression of LH in the PT during the follicular phase. Since in day-active species nocturnal accumulation of LH protein in the pituitary precedes the LH surge, this lowering of LH content may delay or disturb the surge occurrence. Suppression of LH secretion could have resulted from the decreased sensitivity of the PT on the action of GnRH because inflammation reduced GnRH receptor expression. The study suggests that the ability of endotoxin to suppress LH synthesis in the PT may be another mechanism by which inflammation disturbs reproductive neuroendocrine axis in seasonal breeders.

Increased type II transforming growth factor-β receptor expression in liver cells during cholesterol challenge

2000 ◽  
Vol 152 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Giovanna Baccante ◽  
Gabriella Mincione ◽  
Concetta Di Febbo ◽  
Anna Coppa ◽  
Domenico Angelucci ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Liver Cells ◽  
Receptor Expression ◽  
Type Ii ◽  
Β Receptor

Reversible ubiquitination regulates the Smad/TGF-β signalling pathway

2006 ◽  
Vol 34 (5) ◽  
pp. 761-763 ◽  
Author(s):  
S.J. Wicks ◽  
T. Grocott ◽  
K. Haros ◽  
M. Maillard ◽  
P. ten Dijke ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Serine Threonine Kinase ◽  
Full Spectrum ◽  
Threonine Kinase ◽  
Pathological Conditions ◽  
C Terminus ◽  
Β Receptor ◽  
Fine Tune

TGF-β (transforming growth factor-β) signals through serine/threonine kinase receptors and intracellular Smad transcription factors. An important regulatory step involves specific ubiquitination by Smurfs (Smad–ubiquitin regulatory factors), members of the HECT (homologous to E6-associated protein C-terminus) ubiquitin ligase family, which mediate the proteasomal degradation of Smads and/or receptors. Recently, we have defined a novel interaction between Smads and UCH37 (ubiquitin C-terminal hydrolase 37), a DUB (de-ubiquitinating enzyme) that could potentially counteract Smurf-mediated ubiquitination. We have demonstrated specific interactions between UCH37 and inhibitory Smad7, as well as weaker associations with Smad2 and Smad3. Importantly, Smad7 can act as an adaptor able to recruit UCH37 to the type I TGF-β receptor. Consequently, UCH37 dramatically up-regulates TGF-β-dependent gene expression by de-ubiquitinating and stabilizing the type I TGF-β receptor. Our findings suggest that competing effects of ubiquitin ligases and DUBs in complex with Smad7 can serve to fine-tune responses to TGF-βs under various physiological and pathological conditions. Studies are currently under way using activity-based HA (haemagglutinin)-tagged ubiquitin probes to identify the full spectrum of DUBs that impact on Smad/TGF-β signalling activity.

Sign in / Sign up

Export Citation Format

Share Document