scholarly journals Neurokinin B and the Control of the Gonadotropic Axis in the Rat: Developmental Changes, Sexual Dimorphism, and Regulation by Gonadal Steroids

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4818-4829 ◽  
Author(s):  
F. Ruiz-Pino ◽  
V. M. Navarro ◽  
A. H. Bentsen ◽  
D. Garcia-Galiano ◽  
M. A. Sanchez-Garrido ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Sex Steroids ◽  
Developmental Stages ◽  
Female Rats ◽  
Sex Steroid ◽  
Adult Males ◽  
Neurokinin B ◽  
Male And Female Rats ◽  
Gonadotropic Axis ◽  
Key Aspects

Abstract Neurokinin B (NKB), encoded by Tac2 in rodents, and its receptor, NK3R, have recently emerged as important regulators of reproduction; NKB has been proposed to stimulate kisspeptin output onto GnRH neurons. Accordingly, NKB has been shown to induce gonadotropin release in several species; yet, null or even inhibitory effects of NKB have been also reported. The basis for these discrepant findings, as well as other key aspects of NKB function, remains unknown. We report here that in the rat, LH responses to the NK3R agonist, senktide, display a salient sexual dimorphism, with persistent stimulation in females, regardless of the stage of postnatal development, and lack of LH responses in males from puberty onward. Such dimorphism was independent of the predominant sex steroid after puberty, because testosterone administration to adult females failed to prevent LH responses to senktide, and LH responsiveness was not restored in adult males treated with estradiol or the nonaromatizable androgen, dihydrotestosterone. Yet, removal of sex steroids by gonadectomy switched senktide effects to inhibitory, both in adult male and female rats. Sexual dimorphism was also evident in the numbers of NKB-positive neurons in the arcuate nucleus (ARC), which were higher in adult female rats. This is likely the result of differences in sex steroid milieu during early periods of brain differentiation, because neonatal exposures to high doses of estrogen decreased ARC NKB neurons at later developmental stages. Likewise, neonatal estrogenization resulted in lower serum LH levels that were normalized by senktide administration. Finally, we document that the ability of estrogen to inhibit hypothalamic Tac2 expression seems region specific, because estrogen administration decreased Tac2 levels in the ARC but increased them in the lateral hypothalamus. Altogether, our data provide a deeper insight into relevant aspects of NKB function as major regulator of the gonadotropic axis in the rat, including maturational changes, sexual dimorphism, and differential regulation by sex steroids.

scholarly journals Sex-specific maturational trajectory of endocannabinoid plasticity in the rat prefrontal cortex

2020 ◽  
Author(s):  
Axel Bernabeu ◽  
Anissa Bara ◽  
Antonia Manduca ◽  
Milene Borsoi ◽  
Olivier Lassalle ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Plasticity ◽  
Developmental Stages ◽  
Long Term Potentiation ◽  
Female Rats ◽  
Adult Males ◽  
Juvenile Period ◽  
Cross Sectional ◽  
Male And Female Rats

AbstractThe prefrontal cortex (PFC) develops until early adulthood in rodents and humans, but how synaptic plasticity evolves throughout postnatal development is not known. Here, we used a cross-sectional approach to establish the postnatal maturational trajectories of intrinsic properties and synaptic plasticity in the PFC of rats of both sexes. We found that while layer 5 PFC pyramidal neurons from rats of both sexes displayed similar current-voltage relationships, rheobases and resting potentials across all age groups, excitability was lower in female adults compared to the other developmental stages. NMDAR-dependent long-term potentiation and mGluR2/3-mediated long-term depression (LTD) were equally expressed at the juvenile, pubescent and adult developmental stages in animals of both sexes. However, the developmental course of endocannabinoid (eCB)-mediated LTD was sexually dimorphic. First, eCB-LTD emerged during the juvenile period in females. However, although CB1Rs were functional in both sexes at all developmental stages, eCB-LTD’s first emerged during pubescence in male. Second, eCB-LTD engaged distinct receptors in males and females depending on their developmental stages. Female rats employ both CB1R and TRPV1R to produce eCB-LTD at the juvenile stage but solely CB1R at pubescence followed by only TRPV1R at adulthood. In contrast, in pubescent and adult males eCB-LTD always and exclusively depended on CB1R. Pharmacological blockade of 2AG’s principal degrading enzyme allowed incompetent male juvenile synapses to express eCB-LTD. The data reveal different maturational trajectories in the PFC of male and female rats and provide new cellular substrates to the sex-specific behavioral and synaptic abnormalities caused by adolescent exposure to cannabinoids.

scholarly journals Sex Differences in Seoul Virus Infection Are Not Related to Adult Sex Steroid Concentrations in Norway Rats

2000 ◽  
Vol 74 (17) ◽  
pp. 8213-8217 ◽  
Author(s):  
Sabra L. Klein ◽  
Brian H. Bird ◽  
Gregory E. Glass
Keyword(s):  
Sex Differences ◽  
Sex Steroids ◽  
Hormone Treatment ◽  
Female Rats ◽  
Sex Steroid ◽  
Hantavirus Infection ◽  
Male And Female ◽  
Virus Shedding ◽  
Seoul Virus ◽  
Male And Female Rats

ABSTRACT Field studies of hantavirus infection in rodents report that a higher percentage of infected individuals are males than females. To determine whether males were more susceptible to hantavirus infection than females, adult male and female Long Evans rats (Rattus norvegicus) were inoculated with doses of Seoul virus ranging from 10−4 to 106 PFU. The 50% infective doses (ID50) were not significantly different for male and female rats (100.05 and 100.8 PFU, respectively). To determine whether sex differences in response to infection were related to circulating sex steroid hormones, sex steroid concentrations were manipulated and antibody responses and virus shedding were assessed following inoculation with the ID90. Regardless of hormone treatment, males had higher anti-Seoul virus immunoglobulin G (IgG) and IgG2a (i.e., Th1) responses than females and IgG1 (i.e., Th2) responses similar to those of females. Males also shed virus in saliva and feces longer than females. Manipulation of sex steroids in adulthood did not alter immune responses or virus shedding, suggesting that sex steroids may organize adult responses to hantavirus earlier during ontogeny.

scholarly journals Effects and Interactions of Tachykinins and Dynorphin on FSH and LH Secretion in Developing and Adult Rats

Endocrinology ◽  
2014 ◽  
Vol 156 (2) ◽  
pp. 576-588 ◽  
Author(s):  
F. Ruiz-Pino ◽  
D. Garcia-Galiano ◽  
M. Manfredi-Lozano ◽  
S. Leon ◽  
M. A. Sánchez-Garrido ◽  
...  
Keyword(s):  
Substance P ◽  
Opioid Receptor ◽  
Female Rats ◽  
Neurokinin A ◽  
Adult Males ◽  
Neurokinin B ◽  
Gonadotropin Secretion ◽  
Postnatal Maturation ◽  
Male And Female Rats ◽  
Lh Secretion

Kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which coexpress kisspeptins (Kps), neurokinin B (NKB), and dynorphin (Dyn), regulate gonadotropin secretion. The KNDy model proposes that NKB (a stimulator, through NK3R) and Dyn (an inhibitor, through κ-opioid receptor) shape Kp secretion onto GnRH neurons. However, some aspects of this paradigm remain ill defined. Here we aimed to characterize the following: 1) the effects of NKB signaling on FSH secretion and 2) the role of Dyn in gonadotropin secretion after NK3R activation; 3) additionally, we explored the roles of other tachykinin receptors, NK1R and NK2R, on gonadotropin release. Thus, the effects of the NK3R agonist, senktide, on FSH release were explored across postnatal development in male and female rats; gonadotropin responses to agonists of NK1R substance P and NK2R [neurokinin A (NKA)] were also monitored. Moreover, the effects of senktide on gonadotropin secretion were assessed after antagonizing Dyn actions by nor-binaltorphimine didydrochloride. Before puberty, rats of both sexes showed increased FSH secretion to senktide (and Kp-10). Conversely, adult female rats were irresponsive to senktide in terms of FSH, despite proven LH responses, whereas the adult males did not display FSH or LH responses to senktide, even at high doses. In turn, substance P and NKA stimulated gonadotropin secretion in prepubertal rats, whereas in adults modest gonadotropin responses to NKA were detected. By pretreatment with a Dyn antagonist, adult males became responsive to senktide in terms of LH secretion and displayed elevated basal LH and FSH levels; nor-binaltorphimine didydrochloride treatment uncovered FSH responses to senktide in adult females. Furthermore, the expression of Pdyn and Opkr1 (encoding Dyn and κ-opioid receptor, respectively) in the mediobasal hypothalamus was greater in males than in females at prepubertal ages. Overall, our data contribute to refining our understanding on how the elements of the KNDy node and related factors (ie, other tachykinins) differentially participate in the control of gonadotropins at different stages of rat postnatal maturation.

Sex- and age-dependent differences in the hormone and drinking responses to water deprivation

2020 ◽  
Vol 318 (3) ◽  
pp. R567-R578 ◽  
Author(s):  
Susana Quirós Cognuck ◽  
Wagner L. Reis ◽  
Marcia S. Silva ◽  
Gislaine Almeida-Pereira ◽  
Lucas K. Debarba ◽  
...  
Keyword(s):  
Water Deprivation ◽  
Plasma Concentrations ◽  
Female Rats ◽  
Male Rats ◽  
Ang Ii ◽  
Adult Males ◽  
Adaptive Responses ◽  
Male And Female ◽  
Male And Female Rats ◽  
Female Wistar Rats

Maintenance of the volume and osmolality of body fluids is important, and the adaptive responses recruited to protect against osmotic stress are crucial for survival. The objective of this work was to compare the responses that occur in aging male and female rats during water deprivation. For this purpose, groups of male and female Wistar rats aged 3 mo (adults) or 18 mo (old) were submitted to water deprivation (WD) for 48 h. The water and sodium (0.15 M NaCl) intake, plasma concentrations of oxytocin (OT), arginine vasopressin (AVP), corticosterone (CORT), atrial natriuretic peptide (ANP), and angiotensin II (ANG II) were determined in hydrated and water-deprived animals. In response to WD, old male and female rats drank less water and saline than adults, and both adult and old females drank more water and saline than respective males. Dehydrated old animals displayed lower ANG II plasma concentration and CORT response compared with the respective normohydrated rats. Dehydrated adult males had higher plasma ANP and AVP as well as lower CORT concentrations than dehydrated adult females. Moreover, plasma OT and CORT levels of old female rats were higher than those in the dehydrated old male rats. Relative expression of ANG II type 1 receptor mRNA was decreased in the subfornical organ of adult and old male rats as well as adult female rats in response to WD. In conclusion, the study elucidated the effect of sex and age on responses induced by WD, altering the degree of dehydration induced by 48 h of WD.

GONADOTROPHIN PATTERNS IN MALE AND FEMALE RATS: PLASMA LH AND FSH AT VARIOUS AGES EVALUATED BY THE METHOD OF PARABIOSIS

1967 ◽  
Vol 56 (1) ◽  
pp. 165-176 ◽  
Author(s):  
Donald C. Johnson
Keyword(s):  
Follicle Stimulating Hormone ◽  
Chorionic Gonadotrophin ◽  
Female Rats ◽  
Adult Males ◽  
Male And Female ◽  
Ovarian Weight ◽  
Average Value ◽  
Male And Female Rats ◽  
Tonic Level ◽  
Males And Females

ABSTRACT Ventral prostates in hypophysectomized male parabiotic partners of intact animals were used to compare the amount of plasma luteinizing hormone (LH) in males and females of various ages. Ovarian weight, histology, and augmentation with chorionic gonadotrophin, in hypophysectomized androgenized females were used to estimate plasma follicle stimulating hormone (FSH) activity in intact adult males and females. In young animals, up to 50 days of age, males apparently have the same amount of plasma LH as females, but older cyclic females produced significantly heavier prostates in their hypophysectomized male partners than did males. The results are consistent with the interpretation that cyclic surges of LH added to a tonic level produced an average value higher for females than males. In contrast, males of all ages and particularly adults, have a significantly greater amount of circulating FSH than females.

scholarly journals The effects of aging on carbonic anhydrase concentrations in rat liver and skeletal muscle

1988 ◽  
Vol 250 (1) ◽  
pp. 303-305 ◽  
Author(s):  
S Jeffery ◽  
B J Merry ◽  
A M Holehan ◽  
N D Carter
Keyword(s):  
Sexual Dimorphism ◽  
Carbonic Anhydrase ◽  
Slow Muscle ◽  
Female Rats ◽  
Carbonic Anhydrase Ii ◽  
Slow Fibre ◽  
Fast Fibre ◽  
Male And Female Rats ◽  
Effects Of Aging ◽  
Fast Muscles

The isoenzymes carbonic anhydrase II (CAII) and III (CAIII) have been measured by radioimmunoassay in the livers of male and female rats aged from 21 to 800 days. No sexual dimorphism at 21 days was found, but from 50 to 400 days both isoenzymes show sexual differences. From 600 days onwards, these differences are less apparent. CAIII concentrations in two ‘fast’ fibre muscles and one ‘slow’ fibre muscle have been determined. There is no sexual dimorphism in muscle, but a wide variation between individuals was observed. Fast muscles show maximal CAIII levels at 800 days, whereas in slow muscle the concentration of the isoenzyme is declining at this time.

scholarly journals Disparate Changes in Kisspeptin and Neurokinin B Expression in the Arcuate Nucleus After Sex Steroid Manipulation Reveal Differential Regulation of the Two KNDy Peptides in Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (10) ◽  
pp. 3945-3955 ◽  
Author(s):  
Agnete Overgaard ◽  
Francisco Ruiz-Pino ◽  
Juan M. Castellano ◽  
Manuel Tena-Sempere ◽  
Jens D. Mikkelsen
Keyword(s):  
Sex Steroids ◽  
Arcuate Nucleus ◽  
Detailed Examination ◽  
Differential Regulation ◽  
Sex Steroid ◽  
Neurokinin B ◽  
Regulated Expression ◽  
Male Sex ◽  
Specific Regulation ◽  
Kndy Neurons

Abstract Kisspeptin, neurokinin B (NKB) and dynorphin A are coexpressed in a population of neurons in the arcuate nucleus (ARC), termed KNDy neurons, which were recently recognized as important elements for the generation of GnRH pulses. However, the topographic distribution of these peptides and their regulated expression by sex steroids are still not well understood. In this study, detailed examination of NKB and kisspeptin immunoreactivity in the rat ARC was carried out, including comparison between sexes, with and without sex steroid replacement. Neurons expressing kisspeptin and NKB were more prominent in the caudal ARC of females, whereas neurons expressing NKB, but not kisspeptin, were the most abundant in the male. Sex steroid manipulation revealed differential regulation of kisspeptin and NKB; although kisspeptin immunoreactive (ir) cells increased in response to gonadectomy, NKB remained unchanged. Furthermore, the number of NKB-ir cells increased upon sex steroid replacement compared with gonadectomy, whereas kisspeptin did not, suggesting that sex steroids differently regulate these peptides. In addition, only in females did the density of kisspeptin- and NKB-ir fibers in the ARC increase upon sex steroid replacement in relation to sham and ovariectomy, respectively, suggesting sex-specific regulation of release. In conclusion, our observations reveal sex differences in the number of kisspeptin- and NKB-ir cells, which are more prominent in the caudal ARC. The divergent regulation of kisspeptin and NKB peptide contents in the ARC as a function of sex and steroid milieu enlarge our understanding on how these neuropeptides are posttranscriptionally regulated in KNDy neurons.

Gonadal and sex steroid feedback regulation of gonadotrophin mRNA levels and secretion in neonatal male and female rats

1989 ◽  
Vol 3 (2) ◽  
pp. 139-144 ◽  
Author(s):  
P. Pakarinen ◽  
I. Huhtaniemi
Keyword(s):  
Sex Differences ◽  
Feedback Regulation ◽  
Female Rats ◽  
Male Rats ◽  
Sex Steroid ◽  
Mrna Levels ◽  
Negative Feedback Regulation ◽  
Α Subunit ◽  
Male And Female ◽  
Male And Female Rats

ABSTRACT Serum and pituitary LH and FSH, and their pituitary mRNA levels, were measured in neonatal male and female rats after gonadectomy and after gonadectomy with sex steroid replacement. The animals were gonadectomized on day 3 of life, and those given sex steroid replacement were implanted with silicone elastomer capsules containing testosterone for males and diethylstilboestrol for females. Shamoperated rats served as controls. The animals were killed 4 or 8 days later and the sera and pituitaries collected. Pituitary contents of mRNAs for the α subunit, FSH-β and LH-β were determined by blot hybridization using corresponding cDNAs. Distinct sex differences were found in the mRNA responses to gonadectomy and steroid replacement. In the males, gonadectomy increased all mRNA levels at 7 days of age. In the females, a rise on day 7 was detected only for FSH-β; the other mRNAs were increased on day 11 of age. The steroid replacements reversed all the post-gonadectomy increases of mRNAs in both sexes. Moreover, the common α and LH-β mRNAs of the male animals were consistently suppressed below control levels. The serum concentrations of gonadotrophins increased after gonadectomy on day 7 in the males but only on day 11 in the females. The steroid replacements also suppressed the post-gonadectomy increases in serum gonadotrophins, but only the serum concentration of FSH in the females was reduced below controls. Pituitary gonadotrophin concentrations were not affected by gonadectomy, but the steroids suppressed LH in the males and FSH in the females. It is concluded that the onset of negative-feedback regulation of gonadotrophin synthesis by gonads and/or gonadal steroids starts earlier in male rats, before 7 days of age. In female rats these responses appear between 7 and 11 days of age. Clear sex differences were observed in how gonadotrophin mRNAs and pituitary and serum hormone levels responded to gonadectomy and steroid replacement in the neonatal period. Some of the responses differed from those previously reported in adult animals.

Peripheral and Central Sex Steroids Have Differential Effects on the HPA Axis of Male and Female Rats

Stress ◽  
2002 ◽  
Vol 5 (4) ◽  
pp. 235-247 ◽  
Author(s):  
Cheryl M. McCormick ◽  
William Linkroum ◽  
Bethany J. Sallinen ◽  
Nicholas W. Miller
Keyword(s):  
Hpa Axis ◽  
Sex Steroids ◽  
Female Rats ◽  
Male And Female ◽  
Differential Effects ◽  
Male And Female Rats
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