Decreased blood pressure response in mice deficient of the alpha1b-adrenergic receptor.

To investigate the functional role of different alpha1-adrenergic receptor (alpha1-AR) subtypes in vivo, we have applied a gene targeting approach to create a mouse model lacking the alpha1b-AR (alpha1b-/-). Reverse transcription-PCR and ligand binding studies were combined to elucidate the expression of the alpha1-AR subtypes in various tissues of alpha1b +/+ and -/- mice. Total alpha1-AR sites were decreased by 98% in liver, 74% in heart, and 42% in cerebral cortex of the alpha1b -/- as compared with +/+ mice. Because of the large decrease of alpha1-AR in the heart and the loss of the alpha1b-AR mRNA in the aorta of the alpha1b-/- mice, the in vivo blood pressure and in vitro aorta contractile responses to alpha1-agonists were investigated in alpha1b +/+ and -/- mice. Our findings provide strong evidence that the alpha1b-AR is a mediator of the blood pressure and the aorta contractile responses induced by alpha1 agonists. This was demonstrated by the finding that the mean arterial blood pressure response to phenylephrine was decreased by 45% in alpha1b -/- as compared with +/+ mice. In addition, phenylephrine-induced contractions of aortic rings also were decreased by 25% in alpha1b-/- mice. The alpha1b-AR knockout mouse model provides a potentially useful tool to elucidate the functional specificity of different alpha1-AR subtypes, to better understand the effects of adrenergic drugs, and to investigate the multiple mechanisms involved in the control of blood pressure.

Changes in nuclear 3,5,3'-triiodothyronine receptor expression in rat dorsal root ganglia and sciatic nerve during development: comparison with regeneration.

The action of the thyroid hormones on responsive cells in the peripheral nervous system requires the presence of nuclear triiodothyronine receptors (NT3R). These nuclear receptors, including both the alpha and beta subtypes of NT3R, were visualized by immunocytochemistry with the specific 2B3 monoclonal antibody. In the dorsal root ganglia (DRG) of rat embryos, NT3R immunoreactivity was first discretely revealed in a few neurons at embryonic day 14 (E14), then strongly expressed by all neurons at E17 and during the first postnatal week; all DRG neurons continued to possess clear NT3R immunostaining, which faded slightly with age. The peripheral glial cells in the DRG displayed a short-lived NT3R immunoreaction, starting at E17 and disappearing from the satellite and Schwann cells by postnatal days 3 and 7 respectively. In the developing sciatic nerve, Schwann cells also exhibited transient NT3R immunoreactivity restricted to a short period ranging from E17 to postnatal day 10; the NT3R immunostaining of the Schwann cells vanished proximodistally along the sciatic nerve, so that the Schwann cells rapidly became free of detectable NT3R immunostaining. However, after the transection or crushing of an adult sciatic nerve, the NT3R immunoreactivity reappeared in the Schwann cells adjacent to the lesion by 2 days, then along the distal segment in which the axons were degenerating, and finally disappeared by 45 days, when the regenerating axons were allowed to re-occupy the distal segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced vascular contractility in alpha1-adrenergic receptor-deficient mice.

AIM: Alpha1-adrenergic receptors (alpha1-ARs) are classified into three subtypes: alpha1A-AR, alpha1B-AR, and alpha1D-AR. Triple disruption of alpha1A-AR, alpha1B-AR, and alpha1D-AR genes results in hypotension and produces no contractile response of the thoracic aorta to noradrenalin. Presently, we characterized vascular contractility against other vasoconstrictors, such as potassium, prostaglandin F2alpha (PGF(2alpha)) and 5-hydroxytryptamine (5-HT), in alpha1A-AR, alpha1B-AR, and alpha1D-AR triple knockout (alpha1-AR triple KO) mice. MAIN METHODS: The contractile responses to the stimulation with vasoconstrictors were studied using isolated thoracic aorta. KEY FINDINGS: As a result, the phasic and tonic contraction induced by a high concentration of potassium (20 mM) was enhanced in the isolated thoracic aorta of alpha1-AR triple KO mice compared with that of wild-type (WT) mice. In addition, vascular responses to PGF(2alpha) and 5-HT were also enhanced in the isolated thoracic aorta of alpha1-AR triple KO mice compared with WT mice. Similar to in vitro findings with isolated thoracic aorta, in vivo pressor responses to PGF(2alpha) were enhanced in alpha1-AR triple KO mice. Real-time reverse transcription-polymerase chain reaction analysis and western blot analysis indicate that gene expression of the 5-hydroxytryptamine 2A (5-HT(2A)) receptor was up-regulated in the thoracic aorta of alpha1-AR triple KO mice while the prostaglandin F2alpha receptor (FP) was unchanged. SIGNIFICANCE: These results suggest that loss of alpha1-ARs can lead to enhancement of vascular responsiveness to the vasoconstrictors and may imply that alpha1-ARs and the subsequent signaling regulate the vascular responsiveness to other stimulations such as depolarization, 5-HT and PGF(2alpha).

On the existence and function of galanin receptor heteromers in the central nervous system

Galanin receptor (GalR) subtypes 1-3 linked to central galanin neurons may form heteromers with each other and other types of G protein-coupled receptors in the central nervous system (CNS). These heteromers may be one molecular mechanism for galanin peptides and their N-terminal fragments (gal 1-15) to modulate the function of different types of glia-neuronal networks in the CNS, especially the emotional and the cardiovascular networks. GalR-5-HT1A heteromers likely exist with antagonistic GalR-5-HT1A receptor-receptor interactions in the ascending midbrain raphe 5-HT neuron systems and their target regions. They represent a novel target for antidepressant drugs. Evidence is given for the existence of GalR1-5-HT1A heteromers in cellular models with trans-inhibition of the protomer signaling. A GalR1-GalR2 heteromer is proposed to be a galanin N-terminal fragment preferring receptor (1-15) in the CNS. Furthermore, a GalR1-GalR2-5-HT1A heterotrimer is postulated to explain why only galanin (1-15) but not galanin (1-29) can antagonistically modulate the 5-HT1A receptors in the dorsal hippocampus rich in gal fragment binding sites. The results underline a putative role of different types of GalR-5-HT1A heteroreceptor complexes in depression. GalR antagonists may also have therapeutic actions in depression by blocking the antagonistic GalR-NPYY1 receptor interactions in putative GalR-NPYY1 receptor heteromers in the CNS resulting in increases in NPYY1 transmission and antidepressant effects. In contrast the galanin fragment receptor (a postulated GalR1-GalR2 heteromer) appears to be linked to the NPYY2 receptor enhancing the affinity of the NPYY2 binding sites in a putative GalR1-GalR2-NPYY2 heterotrimer. Finally, putative GalR-α2-adrenoreceptor heteromers with antagonistic receptor-receptor interactions may be a widespread mechanism in the CNS for integration of galanin and noradrenaline signals also of likely relevance for depression

Gamma oscillations in V1 are correlated with GABAA receptor density: A multi-modal MEG and Flumazenil-PET study.

High-frequency oscillations in the gamma-band reflect rhythmic synchronization of spike timing in active neural networks. The modulation of gamma oscillations is a widely established mechanism in a variety of neurobiological processes, yet its neurochemical basis is not fully understood. Modeling, in-vitro and in-vivo animal studies suggest that gamma oscillation properties depend on GABAergic inhibition. In humans, search for evidence linking total GABA concentration to gamma oscillations has led to promising -but also to partly diverging- observations. Here, we provide the first evidence of a direct relationship between the density of GABAA receptors and gamma oscillatory gamma responses in human primary visual cortex (V1). By combining Flumazenil-PET (to measure resting-levels of GABAA receptor density) and MEG (to measure visually-induced gamma oscillations), we found that GABAA receptor densities correlated positively with the frequency and negatively with amplitude of visually-induced gamma oscillations in V1. Our findings demonstrate that gamma-band response profiles of primary visual cortex across healthy individuals are shaped by GABAA-receptor-mediated inhibitory neurotransmission. These results bridge the gap with in-vitro and animal studies and may have future clinical implications given that altered GABAergic function, including dysregulation of GABAA receptors, has been related to psychiatric disorders including schizophrenia and depression.

Distribution of the a2, a3, and a5 nicotinic acetylcholine receptor subunits in the chick brain

Nicotinic acetylcholine receptors (nAChRs) are ionotropic receptors comprised of a and ß subunits. These receptors are widely distributed in the central nervous system, and previous studies have revealed specific patterns of localization for some nAChR subunits in the vertebrate brain. In the present study we used immunohistochemical methods and monoclonal antibodies to localize the a2, a3, and a5 nAChR subunits in the chick mesencephalon and diencephalon. We observed a differential distribution of these three subunits in the chick brain, and showed that the somata and neuropil of many central structures contain the a5 nAChR subunit. The a2 and a3 subunits, on the other hand, exhibited a more restricted distribution than a5 and other subunits previously studied, namely a7, a8 and ß2. The patterns of distribution of the different nAChR subunits suggest that neurons in many brain structures may contain several subtypes of nAChRs and that in a few regions one particular subtype may determine the cholinergic nicotinic responses

The bradycardic and hypotensive responses to serotonin are reduced by activation of GABA A receptors in the nucleus tractus solitarius of awake rats

We investigated the effects of bilateral injections of the GABA receptor agonists muscimol (GABA A) and baclofen (GABA B) into the nucleus tractus solitarius (NTS) on the bradycardia and hypotension induced by iv serotonin injections (5-HT, 2 µg/rat) in awake male Holtzman rats. 5-HT was injected in rats with stainless steel cannulas implanted bilaterally in the NTS, before and 5, 15, and 60 min after bilateral injections of muscimol or baclofen into the NTS. The responses to 5-HT were tested before and after the injection of atropine methyl bromide. Muscimol (50 pmol/50 nl, N = 8) into the NTS increased basal mean arterial pressure (MAP) from 115 ± 4 to 144 ± 6 mmHg, did not change basal heart rate (HR) and reduced the bradycardia (-40 ± 14 and -73 ± 26 bpm at 5 and 15 min, respectively, vs -180 ± 20 bpm for the control) and hypotension (-11 ± 4 and -14 ± 4 mmHg, vs -40 ± 9 mmHg for the control) elicited by 5-HT. Baclofen (12.5 pmol/50 nl, N = 7) into the NTS also increased basal MAP, but did not change basal HR, bradycardia or hypotension in response to 5-HT injections. Atropine methyl bromide (1 mg/kg body weight) injected iv reduced the bradycardic and hypotensive responses to 5-HT injections. The stimulation of GABA A receptors in the NTS of awake rats elicits a significant increase in basal MAP and decreases the cardiac Bezold-Jarisch reflex responses to iv 5-HT injections.

Glutamate-N-methyl-D-aspartate receptor modulation and minocycline for the treatment of patients with schizophrenia: an update

Growing consistent evidence indicates that hypofunction of N-methyl-D-aspartate (NMDA) transmission plays a pivotal role in the neuropathophysiology of schizophrenia. Hence, drugs which modulate NMDA neurotransmission are promising approaches to the treatment of schizophrenia. The aim of this article is to review clinical trials with novel compounds acting on the NMDA receptor (NMDA-R). This review also includes a discussion and translation of neuroscience into schizophrenia therapeutics. Although the precise mechanism of action of minocycline in the brain remains unclear, there is evidence that it blocks the neurotoxicity of NMDA antagonists and may exert a differential effect on NMDA signaling pathways. We, therefore, hypothesize that the effects of minocycline on the brain may be partially modulated by the NMDA-R or related mechanisms. Thus, we have included a review of minocycline neuroscience. The search was performed in the PubMed, Web of Science, SciELO, and Lilacs databases. The results of glycine and D-cycloserine trials were conflicting regarding effectiveness on the negative and cognitive symptoms of schizophrenia. D-serine and D-alanine showed a potential effect on negative symptoms and on cognitive deficits. Sarcosine data indicated a considerable improvement as adjunctive therapy. Finally, minocycline add-on treatment appears to be effective on a broad range of psychopathology in patients with schizophrenia. The differential modulation of NMDA-R neurosystems, in particular synaptic versus extrasynaptic NMDA-R activation and specific subtypes of NMDA-R, may be the key mediators of neurogenesis and neuroprotection. Thus, psychotropics modulating NMDA-R neurotransmission may represent future monotherapy or add-on treatment strategies in the treatment of schizophrenia.

In vivo photorelease of GABA in the mouse cortex

Electrical stimulation has been used for more than 100 years in neuroscientific and biomedical research as a powerful tool for controlled perturbations of neural activity. Despite quickly driving neuronal activity, this technique presents some important limitations, such as the impossibility to activate or deactivate specific neuronal populations within a single stimulation site. This problem can be avoided by pharmacological methods based on the administration of receptor ligands able to cause specific changes in neuronal activity. However, intracerebral injections of neuroactive molecules inherently confound the dynamics of drug diffusion with receptor activation. Caged compounds have been proposed to circumvent this problem, for spatially and temporally controlled release of molecules. Caged compounds consist of a protecting group and a ligand made inactive by the bond between the two parts. By breaking this bond with light of an appropriate wavelength, the ligand recovers its activity within milliseconds. To test these compounds in vivo, we recorded local field potentials (LFPs) from the cerebral cortex of anesthetized female mice (CF1, 60-70 days, 20-30 g) before and after infusion with caged γ-amino-butyric-acid (GABA). After 30 min, we irradiated the cortical surface with pulses of blue light in order to photorelease the caged GABA and measure its effect on global brain activity. Laser pulses significantly and consistently decreased LFP power in four different frequency bands with a precision of few milliseconds (P < 0.000001); however, the inhibitory effects lasted several minutes (P < 0.0043). The technical difficulties and limitations of neurotransmitter photorelease are presented, and perspectives for future in vivo applications of the method are discussed.

Decreased GyBAA Receptor Function in the Brain Stem during Pancreatic Regeneration in Rats

Gamma amino outyric acid is a major inhibitory neurotrarsr titter in the central nervous system. In the preset study sv, Have investigate(' the alteration of GABA receptor, In t he hrain stem of rats during pancreatic regeneration. Three groups of rats were used for the study: sham operated, 72 It and 7 days partially pancreatectonnsea. GABA was (juan- (ified by [H]GABA receptor iispiacement method. GABA receptor kin: 10, pat at i et•ers were studied by using the binding of F'.](iAhA as ligand to the Triton X-100 treated me,i1,;-:mes a1,J displacement with unlabelled GABA. GhRA,v receptor activity was studied by using the [` -1 h3cuculline and displacement with unlabellecV euculline. ;.\13A content significantly decreased (1' < (1.(101 ) it, 0-e brain stern during the regeneration of pancreas. 'I hl, high affinity (IAI3A receptor binding sho?:ed it sigii'f cant decrease in 131„.,\ (P < 11.01) and K,I 1).05) n 72 h and 7 days after partial pancreatee 'timv. ";:flhicuculline hin(Iing showed it signih eat, 'le ( r(, :,e in /Jn1,s and K,I (P < 0.001) in 72 h pa^.rcreaw,, mised rats when compared with sham wt--tt' as P,n and K,I reversed to near sham after 7 da,s of pancreatectomv. The results sugge,) that GAB A throur,r; ('GABA receptors in brain Atcem has a regulatory uie during active regeneration of pancreas which will have inunense clinical significance in the treatment of cliahetcs.

Hepatic GABAA receptor functional regulation during rat liver cell proliferation

Gamma aminohutyric acid (GAB A.) receptor tunctionaI status was artaIV se(l in pa It ial hcpatcctoIn ised.II'II). lead nitrate (LN) induced hyperplastic and N-nifrosodiethylantinc INDEAI treated nctplastic rat Iivers during peak DNA synthesis. The high-affinity I'HJGALA binding significantly decreased in PII and NDEi\ rats and the receptor affinity decreased in NDEA and increased in LN rats compared with control . in NDEA. displacement analysis of I'I IIGABA with muscimol showed loss of low-allinity site and a shill of high-allinity cite towards low-allinity . ' 1 he affinity sites shifted towards high-affinity in LN rats. 'file number of low-allinity 1'I Ilhicuc)lline receptors decreased cignilic:uttly in NDEA and I'll whereas it increased in LN rats. (ir\Bi\t receptor :gunist. unrscinrul. disc dependcnllyinhihilcd epidermal growth factor IEGI--) induced DNA synthesis :uul enhanced the tr:utsfnrnting grmvth )actor (Il I I'(il (tlI mediated DNA synthesis suppression in prim:uy hepalucvte cultures . Our results suggest that GABA,t reccjhtor act as an inhibitory signal fur hepatic cell prolifctatiun.

Enhancement Of High Affinity Y-Aminobutyric Acid Receptor Binding In Cerebellum Of Pyridoxine-Deficient Rat

The high-affinity of [3H]y-aminobutyric acid (GABA) to GABAA receptors and [3H]baclofen to GABAB receptors were studied in the cerebellum of pyridoxine-deficient rats and compared to pyridoxine-supplemented controls. There was a significant increase in the maximal binding ( Bmax) of both GABAA and GABAB receptors with no significant difference in their binding affinities (Kd). The changes observed suggest a supersensitivity of GABAA and GABAB receptors which seems to correlate negatively with the concentration of GABA in the cerebellum of pyridoxine-deficient rats.

Análisis del gen adra2a receptor alfa 2a adrenergico en pacientes con trastorno de hiperactividad y déficit de atención

El trastorno de hiperactividad y déficit de atención (THDA), es definido clínicamente como una alteración en el comportamiento, caracterizada por inatención, hiperactividad e impulsividad. Estos aspectos son clasificados en tres subtipos, que son: Inatento, hiperactivo impulsivo y mixto. Clínicamente se describe un espectro amplio que incluye desordenes académicos, trastornos de aprendizaje, déficit cognitivo, trastornos de conducta, personalidad antisocial, pobres relaciones interpersonales y aumento de la ansiedad, que pueden continuar hasta la adultez. A nivel global se ha estimado una prevalencia entre el 1% y el 22%, con amplias variaciones, dadas por la edad, procedencia y características sociales. En Colombia, se han realizado estudios en Bogotá y Antioquia, que han permitido establecer una prevalencia del 5% y 15%, respectivamente. La causa específica no ha sido totalmente esclarecida, sin embargo se ha calculado una heredabilidad cercana al 80% en algunas poblaciones, demostrando el papel fundamental de la genética en la etiología de la enfermedad. Los factores genéticos involucrados se relacionan con cambios neuroquímicos de los sistemas dopaminérgicos, serotoninérgicos y noradrenérgicos, particularmente en los sistemas frontales subcorticales, corteza cerebral prefrontal, en las regiones ventral, medial, dorsolateral y la porción anterior del cíngulo. Basados en los datos de estudios previos que sugieren una herencia poligénica multifactorial, se han realizado esfuerzos continuos en la búsqueda de genes candidatos, a través de diferentes estrategias. Particularmente los receptores Alfa 2 adrenérgicos, se encuentran en la corteza cerebral, cumpliendo funciones de asociación, memoria y es el sitio de acción de fármacos utilizados comúnmente en el tratamiento de este trastorno, siendo esta la principal evidencia de la asociación de este receptor con el desarrollo del THDA. Hasta la fecha se han descrito más de 80 polimorfismos en el gen (ADRA2A), algunos de los cuales se han asociado con la entidad. Sin embargo, los resultados son controversiales y varían según la metodología diagnóstica empleada y la población estudiada, antecedentes y comorbilidades. Este trabajo pretende establecer si las variaciones en la secuencia codificante del gen ADRA2A, podrían relacionarse con el fenotipo del Trastorno de Hiperactividad y el Déficit de Atención.

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

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-beta (TGF beta) 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 (similar to 40 turn). Ovaries were collected (n=16) from inid-sequence hens maintained on a long-day photoschedule (16h 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 niRNA 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 nun, before filling to F3/2; levels then rose sharply (3-fold) to F1 levels. Granulosa betaglycan niRNA expression rose 3-fold from 4-5(.)9 min 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 nim to F3, ActRIIB expression increased significantly (2-fold) from F3 to F1 and ActIIA, increased 22-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 filling similar to 50% in the F I. In all follicles studied expression of betaglycan and ActRI (granulosa: 1-0(.)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; ActR(.) 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.

Variation in pituitary expression of mRNAs encoding the putative inhibin co-receptor (betaglycan) and type-I and type-II activin receptors during the chicken ovulatory cycle

Secretion of LH and FSH from the anterior pituitary is regulated primarily by hypothalamic GnRH and ovarian steroid hormones. More recent evidence indicates regulatory roles for certain members of the transforming growth factor beta (TGF beta) superfamily including inhibin and activin. The aim of this study was to identify expression of mRNAs encoding key receptors and ligands of the inhibin/activin system in the hen pituitary gland and to monitor their expression throughout the 24-25-h ovulatory cycle. Hens maintained on long days (16 h light/8 h dark) were killed 20, 12, 6 and 2 h before predicted ovulation of a midsequence egg (n = 8 per group). Anterior pituitary glands were removed, RNA extracted and cDNA synthesized. Plasma concentrations of LH, FSH, progesterone and inhibin A were measured. Real-time quantitative PCR was used to quantify pituitary expression of mRNAs encoding betaglycan, activin receptor (ActR) subtypes (type I, IIA), GnRH receptor (GnP,H-R), LH beta subunit, FSH beta subunit and GAPDH. Levels of mRNA for inhibin/activin beta A and beta B subunits, inhibin alpha subunit, follistatin and ActRIIB mRNA in pituitary were undetectable by quantitative PCR (< 2 amol/reaction). Significant changes in expression (P < 0.05) of ActRIIA and betaglycan mRNA were found, both peaking 6 h before ovulation just prior to the preovulatory LH surge and reaching a nadir 2 h before ovulation, just after the LH surge. There were no significant changes in expression of ActRI mRNA throughout the cycle although values were correlated with mRNA levels for both ActRIIA (r=0.77; P < 0.001) and betaglycan (r=0.45; P < 0.01). Expression of GnRH-R mRNA was lowest 20 h before ovulation and highest (P < 0.05) 6 h before ovulation; values were weakly correlated with betaglycan (r=0.33; P=0.06) and ActRIIA (r=0.34; P=0.06) mRNA levels. Expression of mRNAs encoding LH beta and FSH beta subunit were both lowest (P < 0.05) after the LH surge, 2 h before ovulation. These results are consistent with an endocrine, but not a local intrapituitary, role of inhibin-related proteins in modulating gonadotroph function during the ovulatory cycle of the hen, potentially through interaction with betaglycan and ActRIIA. In contrast to mammals, intrapituitary expression of inhibin/activin subunits and follistatin appears to be extremely low or absent in the domestic fowl.