scholarly journals Sexually dimorphic effects of morphine and MK-801: sex steroid-dependent and -independent mechanisms

2002 ◽  
Vol 92 (2) ◽  
pp. 493-503 ◽  
Author(s):  
Deborah N. D'Souza ◽  
Richard E. Harlan ◽  
Meredith M. Garcia
Keyword(s):  
Gender Differences ◽  
Sex Steroids ◽  
Behavioral Responses ◽  
Gonadal Steroids ◽  
Sex Steroid ◽  
Sexually Dimorphic ◽  
Mk 801 ◽  
Aspartate Receptor ◽  
Steroid Dependent

Rats show gender differences in responses to morphine and the N-methyl-d-aspartate receptor antagonist dizocilpine (MK-801); the role of sex steroids in mediating these differences is unclear. We tested the overall hypothesis that circulating gonadal steroids determine the gender differences in morphine- and MK-801-induced behavior and c-Fos expression. Morphine caused a greater expression of c-Fos in the striatum of intact males than of that females, which was independent of sex steroids. MK-801 completely inhibited morphine-induced c-Fos in intact females but only caused partial inhibition in intact males; castrated males showed complete inhibition, which was reversed by testosterone, but gonadal steroids had no effect on this response in females. In thalamus, there was a large sex difference in the response to MK-801 that was independent of gonadal steroids. Behavioral responses to morphine were greater in males, but responses to MK-801 were greater in females; both were sex steroid independent. These findings show significant sex differences in response to morphine and MK-801 that are mediated by sex steroid-dependent and -independent mechanisms, which may be important in treatment outcomes of drug addiction.

scholarly journals Sex Steroids and the Shaping of the Peripubertal Brain: The Sexual-Dimorphic Set-Up of Adult Neurogenesis

2021 ◽  
Vol 22 (15) ◽  
pp. 7984
Author(s):  
Sara Trova ◽  
Serena Bovetti ◽  
Sara Bonzano ◽  
Silvia De Marchis ◽  
Paolo Peretto
Keyword(s):  
Adult Neurogenesis ◽  
Sex Steroids ◽  
Neural Circuits ◽  
High Sensitivity ◽  
Brain Regions ◽  
Current Data ◽  
Sex Steroid ◽  
Sexually Dimorphic ◽  
Steroid Dependent ◽  
Set Up

Steroid hormones represent an amazing class of molecules that play pleiotropic roles in vertebrates. In mammals, during postnatal development, sex steroids significantly influence the organization of sexually dimorphic neural circuits underlying behaviors critical for survival, such as the reproductive one. During the last decades, multiple studies have shown that many cortical and subcortical brain regions undergo sex steroid-dependent structural organization around puberty, a critical stage of life characterized by high sensitivity to external stimuli and a profound structural and functional remodeling of the organism. Here, we first give an overview of current data on how sex steroids shape the peripubertal brain by regulating neuroplasticity mechanisms. Then, we focus on adult neurogenesis, a striking form of persistent structural plasticity involved in the control of social behaviors and regulated by a fine-tuned integration of external and internal cues. We discuss recent data supporting that the sex steroid-dependent peripubertal organization of neural circuits involves a sexually dimorphic set-up of adult neurogenesis that in turn could be relevant for sex-specific reproductive behaviors.

The N-methyl-d-aspartate receptor antagonist MK-801 delays the onset of puberty and may acutely block the first spontaneous LH surge and ovulation in the rat

1991 ◽  
Vol 131 (3) ◽  
pp. 435-441 ◽  
Author(s):  
H. M. A. Meijs-Roelofs ◽  
P. Kramer ◽  
E. C. M. van Leeuwen
Keyword(s):  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Acute Treatment ◽  
Physiological Role ◽  
Female Rat ◽  
Mk 801 ◽  
Aspartate Receptor ◽  
Serum Lh ◽  
Lh Secretion

ABSTRACT The physiological role of activated hypothalamic N-methyl-d-aspartate (NMDA) receptors during the final phase of female sexual maturation was explored in the rat. The effects of administration of the specific non-competitive receptor antagonist MK-801 on the occurrence of first ovulation and on LH secretion were studied. Injections of MK-801 (0·1–0·2 mg/kg body wt, s.c.) were given once or twice daily, starting at 28 or 35 days of age and continuing up to the day of first ovulation, resulted in a significant delay of this ovulation. Rats that were treated daily with 0·2 mg MK-801/kg, starting on days 30 or 34 and continuing up to day 38, but not including the day of first pro-oestrus, also showed retarded first ovulation. No decrease in serum LH concentration, compared with control rats, could be detected in these rats. Acute treatment with MK-801 (one or two injections of 0·2, or one injection of 0·5 mg/kg) given at 11.30 h (and 16.00 h) on the day of first pro-oestrus produced partial (1 × 0·2 mg/kg) or complete (2×0·2 and 1 × 0·5 mg/kg) blockade of first ovulation; blocked rats ovulated 1 day later. Serum LH concentrations at 16.00 h on the day of pro-oestrus were significantly decreased in all MK-801-treated groups compared with saline-injected control rats. At 19.00 and 22.00 h LH concentrations remained low in all non-ovulating MK-801-treated rats, but increased in the MK-801-treated rats that ovulated. Thus chronic blockade of the NMDA receptors by the antagonist MK-801 delays but does not prevent first ovulation, whereas acute treatment blocks the pro-oestrous LH peak. It was concluded that activation of NMDA receptors plays an important role both in tonic and preovulatory LH secretion during the onset of puberty in the female rat. Journal of Endocrinology (1991) 131, 435–441

Sex steroids-induced neurogenesis in adult brain: a better look at mechanisms and mediators

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hamideh Abotalebi ◽  
Babak Ebrahimi ◽  
Raziyeh Shahriyari ◽  
Reyhaneh Shafieian
Keyword(s):  
Sex Steroids ◽  
Ventricular Zone ◽  
Mammalian Species ◽  
Adult Brain ◽  
Sex Steroid ◽  
Subgranular Zone ◽  
Human Beings ◽  
The Relationship ◽  
The Brain

Abstract Adult neurogenesis is the production of new nerve cells in the adult brain. Neurogenesis is a clear example of the neuroplasticity phenomenon which can be observed in most of mammalian species, including human beings. This phenomenon occurs, at least, in two regions of the brain: the subgranular zone of the dentate gyrus in hippocampus and the ventricular zone of lateral ventricles. Numerous studies have investigated the relationship between sex steroid hormones and neurogenesis of adult brain; of which, mostly concentrated on the role of estradiol. It has been shown that estrogen plays a significant role in this process through both classic and non-classic mechanisms, including a variety of different growth factors. Therefore, the objective of this review is to investigate the role of female sex steroids with an emphasis on estradiol and also its potential implications for regulating the neurogenesis in the adult brain.

Aromatase, 5α- and 5β-reductase in brain, pituitary and skin of the sex-role reversed Wilson's phalarope

1989 ◽  
Vol 122 (2) ◽  
pp. 573-581 ◽  
Author(s):  
B. A. Schlinger ◽  
A. J. Fivizzani ◽  
G. V. Callard
Keyword(s):  
Sex Role ◽  
Breeding Population ◽  
Role Reversal ◽  
Sex Steroid ◽  
Aromatase Activity ◽  
Sexually Dimorphic ◽  
Sex Role Reversal ◽  
Steroid Dependent ◽  
Generating System ◽  
Wilson’S Phalarope

ABSTRACT While intrasexual competition for mates is generally considered to be an androgen-dependent characteristic of reproductively active males, in the Wilson's phalarope (Phalaropus tricolor) it is the female that acquires the brighter nuptial plumage and aggressively competes for access to the less aggressive males. Despite this pronounced sex-role reversal, circulating sex steroid hormones of breeding phalaropes are similar to those of avian species displaying traditional male–female reproductive roles. To investigate whether these behavioural and morphological steroid-dependent differences may be due to differences in target organ metabolism of circulating androgen, [3H]androstenedione in the presence of an NADPH-generating system was incubated with homogenates of brain, pituitary and skin of male and female Wilson's phalaropes collected from a naturally breeding population. Oestrone, 5α-androstanedione and 5β-androstanedione were measured as endpoints of aromatization, 5α-reduction and 5β-reduction respectively. Aromatase activity in the anterior hypothalamus/preoptic area (AHPOA) and posterior hypothalamus was greater in breeding males with high circulating concentrations of testosterone than in females, and activity in the AHPOA was greater in breeding than in non-breeding males (with low circulating testosterone). Aromatase levels did not differ in septum, archistriatum, hyperstriatum or pituitary. 5α- and 5β-reductase were detected in all neuroendocrine tissues sampled and although there were no significant male–female differences, 5α-reductase was greater in the AHPOA of breeding than of non-breeding males. We infer from this that the behavioural sex-role reversal of phalaropes is unlikely to be accounted for by differences in androgen metabolism in neural targets, although the capacity to form greater quantities of oestrogenic and 5α-reduced metabolites in the AHPOA of breeding males may be linked to the expression of masculine copulatory behaviours. Aromatase activity was not detected in skin containing a sexually dimorphic feather tract; however, 5α- and 5β-reductase activities were significantly higher in females than in males and may account for the brighter nuptial plumage of females. These data suggest that alternate determinants of neural responsiveness such as sex-steroid receptor abundance or neural circuitry may underlie atypical sexual behaviours in phalaropes. Journal of Endocrinology (1989) 122, 573–581

Effects of orchidectomy and sex steroids on vasopressin response to dehydration

1982 ◽  
Vol 99 (4) ◽  
pp. 493-499 ◽  
Author(s):  
G. Valiquette ◽  
L. Martini
Keyword(s):  
Sex Steroids ◽  
Water Deprivation ◽  
Gonadal Steroids ◽  
The Other ◽  
Male Rats ◽  
Sex Steroid ◽  
Short Term ◽  
Vasopressin Secretion ◽  
Hypothalamic Level

Abstract. The secretion of vasopressin has been shown recently to be influenced by gonadal steroids. To further evaluate the relevance of sex steroids in the control of vasopressin secretion, the vasopressin response to dehydration has been studied in normal, castrated and sex-steroid treated castrated male rats. Short-term (3 weeks) castration did not modify the vasopressin response to 48 h of water deprivation. Long-term (10 weeks) castration, on the other hand, consistently reduced the vasopressin response by more than 50%. In both cases, the osmolality was unaffected. Treatment of long-term castrated rats with testosterone, dihydrotestosterone, or oestradiol increased the vasopressin response to dehydration towards normal control levels. However, only oestradiol could restore it to and beyond normal levels, although all three steroids were given in doses that were equipotent in bringing back to normal the plasma LH levels of the castrated animals. Angiotensin-II generation may indirectly be augmented by oestradiol treatment and this may account for the effect of oestradiol here reported. No such mechanism, however, may be invoked in the case of androgens; a direct modulatory effect at the hypothalamic level is postulated for explaining their influence on vasopressin secretion.

170. THE ROLE OF MEGALIN IN PROSTATE DEVELOPMENT OF THE MOUSE

2010 ◽  
Vol 22 (9) ◽  
pp. 88 ◽  
Author(s):  
M. Gamat ◽  
G. Shaw ◽  
M. B. Renfree
Keyword(s):  
Cell Membrane ◽  
Knockout Mice ◽  
Sex Steroids ◽  
Urogenital Sinus ◽  
Sex Steroid ◽  
Testicular Descent ◽  
Mouse Prostate ◽  
Bud Induction ◽  
Bud Initiation

Prostatic development is dependent on androgens; but the precise mechanism by which androgens mediate their effect is still unclear. Megalin, a cell membrane transporter, may shuttle sex steroids into cells to regulate androgen-responsive genes responsible for prostatic bud induction in the urogenital sinus (UGS). In megalin knockout mice, testicular descent fails and the vagina fails to open in females, both of which are dependent on sex steroid signalling (Hammes et al. 2005) . In this megalin-mediated pathway, SHBG-bound sex steroids bind to megalin, which is internalised. The SHBG-sex steroid complex is released, and the sex steroid is released from SHBG where it can bind to the androgen receptor to regulate androgen responsive genes. Receptor-Associated Protein (RAP) is a molecular chaperone protein that protects newly synthesised megalin from binding to potential ligands in the cytoplasm prior to insertion into the cell membrane. We hypothesised that megalin may shuttle SHBG-bound androgens across the cell membrane. This study characterised the expression and evaluated a possible role for megalin in the development of the mouse prostate. Megalin, SHBG and RAP transcripts were detected in the developing male and female UGS of the mouse from day E14.5 to day E18.5 (when prostatic buds start to form) and in the adult prostate. Megalin, SHBG and RAP protein were localised in the urogenital epithelium. To assess the role of megalin in prostatic development, UGS tissues were incubated with androgens in the presence and absence of RAP. Incubating UGS tissues with RAP did NOT inhibit prostatic bud initiation. Furthermore, in the UGS of megalin knockout mice, prostatic bud formation appeared to be identical to those of wild-type littermates. These results demonstrate that megalin is not involved in prostatic bud initiation. However, the ubiquitous expression of megalin suggests that its role is redundant in the prostate. (1) Hammes A et al. (2005) Role of endocytosis in cellular uptake of sex steroids. Cell 122(5), 751–62.

scholarly journals Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease

2000 ◽  
Vol 25 (1) ◽  
pp. 1-16 ◽  
Author(s):  
F Labrie ◽  
V Luu-The ◽  
SX Lin ◽  
J Simard ◽  
C Labrie ◽  
...  
Keyword(s):  
Human Physiology ◽  
Postmenopausal Women ◽  
Sex Steroids ◽  
Sex Steroid ◽  
Peripheral Target ◽  
Adult Men ◽  
Hydroxysteroid Dehydrogenases ◽  
The Family ◽  
Site Of Action

In women and men, an important proportion of estrogens and androgens are synthesized locally at their site of action in peripheral target tissues. This new field of endocrinology has been called intracrinology. In postmenopausal women, 100% of active sex steroids are synthesized in peripheral target tissues from inactive steroid precursors while, in adult men, approximately 50% of androgens are made locally in intracrine target tissues. The last and key step in the formation of all estrogens and androgens is catalyzed by members of the family of 17beta-hydroxysteroid dehydrogenases (17 beta-HSDs) while different 17 beta-HSDs inactivate these steroids in the same cell where synthesis takes place. To date, seven human 17 beta-HSDs have been cloned, sequenced and characterized. The 17 beta-HSDs provide each cell with the means of precisely controlling the intracellular concentration of each sex steroid according to local needs.

scholarly journals Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men

2006 ◽  
Vol 290 (5) ◽  
pp. E1006-E1013 ◽  
Author(s):  
Thomas Münzer ◽  
Clifford J. Rosen ◽  
S.Mitchell Harman ◽  
Katherine M. Pabst ◽  
Carol St. Clair ◽  
...  
Keyword(s):  
Sex Steroids ◽  
Hormone Replacement ◽  
Sex Steroid ◽  
Sexually Dimorphic ◽  
Hormone Administration ◽  
Igf I ◽  
Cross Links ◽  
Paracrine Actions ◽  
Tissue Production ◽  
Igfbp 3

Circulating GH, IGF-I, IGFBP-3, and sex steroid concentrations decrease with age. GH or sex steroid treatment increases IGFBP-3, but little is known regarding the effects of these hormones on other IGFBPs. We assessed the effects of 26 wk of administration of GH, sex steroids, or GH + sex steroids on AM levels of IGF-I, IGFBPs 1–5, insulin, glucose, and osteocalcin and 2-h urinary excretion of deoxypyridinolline (DPD) cross-links in 53 women and 71 men aged 65–88 yr. Before treatment, in women and men, IGF-I was directly related to IGFBP-3 ( P < 0.001 and P < 0.0001) and IGFBP-1 to IGFBP-2 ( P = 0.0001). In women, IGFBP-1 was inversely related to insulin ( P < 0.0005) and glucose ( P < 0.005) and IGFBP-4 to osteocalcin ( P < 0.01). IGFBP-4 and IGFBP-5 were not significantly related to DPD cross-links. GH and/or sex steroid increased IGF-I levels in both sexes, with higher concentrations in men ( P < 0.001). In women, the IGF-I increment after GH was attenuated by hormone replacement therapy (HRT) coadministration ( P < 0.05). Hormone administration also increased IGFBP-3. IGFBP-1 was unaffected by GH + sex steroids, whereas GH decreased IGFBP-2 by 15% in men ( P < 0.05). Hormone administration did not change IGFBP-4, whereas in men IGFBP-5 increased by 20% after GH ( P < 0.05) and 56% after GH + testosterone ( P = 0.0003). These data demonstrate sexually dimorphic IGFBP responses to GH. Additonally, HRT attenuated or prevented GH-mediated increases in IGF-I and IGFBP-3. Whether GH and/or sex steroid administration alters local tissue production of IGFBPs and whether the latter influence autocrine or paracrine actions of IGF-I remain to be determined.

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