Thursday, September 25, 2025

Oxytocin Neurohormones and psychiatric disorders: BPA oxytocin receptor (OTR) disruption

 https://pubmed.ncbi.nlm.nih.gov/34597715/

 concerns were raised with respect to the phrasing of comparisons drawn between humans and animal models. These comparisons were deemed unsupportable,

So was it retracted because the animal "models" were the wrong "models" or because humans are not considered "animals" and thus the comparison in science between humans and animals is no longer valid?

 The authors disagree with the reason for the retraction.

OK let's dig into the paper! 

I was searching transgender neurohormones and that's the paper I got and so the fact that it was retracted intrigued me to no end. I know that females have at least twice as many oxytocin neuroreceptors than males.

 The effect of the dopamine D2-type receptor agonist, quinpirole, was examined on learning-conditioned sexual preference in rats. Males, but not females, learn to exhibit same-sex preference after cohabitation under the effects of quinpirole (Cibrian-Llanderal et al., 2012). Moreover, this effect was facilitated by co-administration of oxytocin (Tri-ana-Del Rio et al., 2015).

 fascinating!!!

  Aripiprazole is an atypical antipsychotic drug with partial agonistic activity at dopamine D2 and D3 receptors, partial agonist to 5-HT1A and antagonist to 5-HT2A receptors (Frankel and Schwartz, 2017). A case report revealed a 28-year-old male patient diagnosed with schizoid personality disorder, who after being treated with aripiprazole, switched from an exclusive heterosexual with poor sexual activity to hypersexuality with homosexual behavior (Mete et al., 2016). Interestingly, two weeks after discontinuing aripiprazole, he ceased his compulsive sexual behavior and reported a return to heterosexual orientation.

 wow - truly stunning!!

Neuroscience & Biobehavioral Reviews

Volume 131, December 2021, Pages 479-488

 Haimei Li, Alonso Fern´andez-Guasti, Yi Xu, Dick Swaab,
RETRACTED: Sexual orientation, neuropsychiatric disorders and the neurotransmitters involved,
Neuroscience & Biobehavioral Reviews,
Volume 131,
2021,
Pages 479-488,
ISSN 0149-7634,
https://doi.org/10.1016/j.neubiorev.2021.09.048.
(https://www.sciencedirect.com/science/article/pii/S0149763421004310)
Abstract: This article has been retracted:

 https://www.cell.com/iscience/fulltext/S2589-0042%2824%2901521-9

 The medial preoptic area (MPOA) of the rat hypothalamus contains the sexually dimorphic nucleus (SDN), which is 2–7 times larger in males than in females (Gorski et al., 1980). The difference in this brain area is related to the early endocrine milieu, thus perinatal androgen produced by the testes in males induces a larger SDN-POA...The SDN of the MPOA appears to be related to sexual preference, because its lesion in male ferrets or rats changes partner preference...

 learning-conditioned same-sex preference could develop by administering quinpirole or oxytocin either alone or together (Triana-Del Rio et al., 2015). Though the number of oxytocin neurons in the paraventricular nucleus did not seem to be related to sexual orientation (Purba et al., 1993), researchers did find oxytocin had stronger impact on social face processing in homosexual men than in heterosexual men. This indicates that oxytocin may play a different role in the regulation of social interactions according to sexual orientation (Thienel et al., 2014).


..............................

 Prevalence of schizophrenia and psychotic illness or episode were higher in gay men and men who were not sure of their sexual orientation (Bolton and Sareen, 2011)....

........................................

  in the Netherlands, where the general attitude towards non-heterosexual orientation is quite positive, there was a higher prevalence of psychiatric disorders among homosexuals, compared with their heterosexual counterparts (Sandfort et al., 2001).

 .......................................

  induced by endocrine manipulations during early development.

..........................................

 several features of schizophrenia, depressed mood and homosexuality are exclusively human-centered concepts.

 medial amygdala kisspeptin neurons could be involved in regulating attraction towards opposite-sex conspecifics as well as experimental anxiety. They found that after selectively stimulating these neurons, there was an increase in the time spent by male mice investigating estrous females....

 ................................

 Maternal exposure to oxytocin during birth has a modest association with risk for autism in male newborns (Weisman et al., 2015). Meanwhile, babies whose mothers take drugs before their birth
not only display withdrawal syndrome after birth, but also could be left with permanent brain damage. Children having intrauterine exposure to cocaine had a decreased head circumference, and exhibited more withdrawn, anxious, and depressed behaviors at 10 years of age (Richardson et al., 2013) as well as less favorable function as adolescents (Buckingham-Howes et al., 2013). These studies suggest that fetal exposure to medication that affects neurotransmitters may increase adverse neuropsychiatric outcome in newborns.

  The high association between psychiatric alterations and non-heterosexual orientation suggests that neurotransmitter changes during development may have an impact on both.
Medications and other chemicals given to pregnant woman may promote the development of neuropsychiatric disorders in the offspring and could lead to individuals with non-heterosexual orientation.

 Borland, J.M., Aiani, L.M., Norvelle, A., Grantham, K.N., O’Laughlin, K., Terranova, J.I.,
Frantz, K.J., Albers, H.E., 2019. Sex-dependent regulation of social reward by oxytocin receptors in the ventral tegmental area. 

 down-regulation of dopamine level results in increased sexual attractiveness of males towards other male flies.

Mutation of Drosophila dopamine receptor DopR leads to male–male courtship behavior

B Chen, H Liu, J Ren, A Guo
Biochemical and biophysical research communications, 2012Elsevier
 
Cibrian-Llanderal, T., Rosas-Aguilar, V., Triana-Del Rio, R., Perez, C.A., Manzo, J.,
Garcia, L.I., Coria-Avila, G.A., 2012. Enhanced D2-type receptor activity facilitates the
development of conditioned same-sex partner preference in male rats. Pharmacol.
Biochem. Behav. 102 (2), 177–183.
 

Perinatal bisphenol A (BPA) exposure alters brain oxytocin receptor (OTR) expression in a sex-and region-specific manner: A CLARITY-BPA consortium follow-up …

SK Witchey, J Fuchs, HB Patisaul - Neurotoxicology, 2019 - Elsevier
Bisphenol A (BPA) is a well-characterized endocrine disrupting chemical (EDC) used in
plastics, epoxy resins and other products. Neurodevelopmental effects of BPA exposure are
a major concern with multiple rodent and human studies showing that early life BPA
exposure may impact the developing brain and sexually dimorphic behaviors. The CLARITY-
BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) program was
established to assess multiple endpoints, including neural, across a wide dose range …
 
 Perinatal Bisphenol A (BPA) Exposure Alters Brain Oxytocin Receptor (OTR) Expression 
 oxytocin receptor (OTR) disruption ...
 the posterior bed nucleus of stria terminalis (BNSTp), ventromedial hypothalamus (VMH), and
the paraventricular hypothalamic nucleus (PVN). ...
 OT is synthesized primarily by the paraventricular (PVN) and supraoptic nuclei (SON) and
released in multiple areas of the mesolimbic dopamine system and other brain nuclei that
play a role in food intake, social recognition, mate choice, anxiety, empathy, parental care
and other socioemotional behaviors (Caldwell, 2017; Carter et al., 2009; Johnson and
Young, 2015; King et al., 2016; Patisaul, 2017).
 Many aspects of the OT signaling pathways are sexually dimorphic and can sex-specifically
influence sociosexual behaviors including anxiety (Caldwell, 2017; Johnson and Young,
2015; King et al., 2016; Scott et al., 2015; Smith et al., 2017). Exquisitely sensitive to
steroid hormones, responsivity of OT and OTR to estrogens and androgens can also be sex
specific. 
For example, in the adult rodent brain, OTR is upregulated by estradiol in the
female ventrolateral portion of the ventromedial nucleus (VMNvl), while
testosterone can
suppress OT release
(Coirini et al., 1992; Johnson, 1992)....
 OTR binding in regions known to be susceptible to estrogen modulation during development, 
As expected, in the control groups OTR binding was sexually dimorphic in the BNSTp (t(13)=5.41, p≤0.001), PVN (t(11)=2.86, p≤0.02), and VMH
(t(17)=3.93, p≤0.001) with
males having higher OTR binding (Table 1). 
 males having greater OTR
binding in BNSTp, VMH and PVN (Smith et al., 2017). These results confirm that we were
sufficiently powered to successfully detect known sex differences, and that these sex
differences are preserved across rat strains. Additionally, we identified sexually dimorphic
OTR binding in the juvenile BNSTld, an outcome which has not been previously reported.
In this region, females have greater OTR expression then males
this corroborates my previous blog posts on how females have much greater oxytocin expression than male mammals - for female bonding with babies! 


BPA exposure included pre- and post-natal windows, including adolescence, when OTR expression and binding levels can be dramatically changing, it is not possible to discern when BPA exposure induced OTR binding disruption.

 OTR binding in the central amygdala, for example, negatively
correlates with social interest in females, while OTR binding in the male MeA positively
correlates with social interest (Dumais et al., 2013). These and other studies emphasize that
different OTR binding densities across regions and sex coordinate different aspects of
socioemotional behaviors including anxiety, alloparental behavior and pair-bond formation
(Carter et al., 2009). OT signaling is also critical for the “GABA switch;” the postnatal
transition of neuronal GABA neurotransmission from excitatory to inhibitory (Tyzio et al.,
2006; Tyzio et al., 2014). There is some evidence that perinatal BPA may disrupt GABA
levels and signaling during this critical transition period but a role for OTR has not been
explored in this context (Franssen et al., 2016; Zalko et al., 2016). OT is also important for
heart development, as well as autonomic regulation of the circulatory system.
Overexpression of OTR in the PVN affects neurogenic control of circulation including
baroreceptor reflex sensitivity and blood pressure variability (Lozic et al., 2014)

 

Perinatal bisphenol A (BPA) exposure alters brain oxytocin receptor (OTR) expression in a sex- and region- specific manner: A CLARITY-BPA consortium follow-up study

 https://www.sciencedirect.com/science/article/abs/pii/S0031938425001349 prenatal exposure to BPA can induce psychotic-like behaviors and impair certain schizophrenia-related GABAergic markers, including GAD67, NRG1, ERbB4, and parvalbumin (PV), in the prefrontal cortex (PFC) of adult offspring rats.

 we set out not only to determine whether exposure altered OTR density within each region, but also if there were instances where exposure altered sex differences in density. 

  OTR expression was quantified by optical density using the digital densitometry

 Densitometry is a method used to measure bone mineral content by analyzing the attenuation of x-ray beams passing through a specimen,

 Male controls had significantly more OTR expression in the BNSTp, PVN and VMH. These sex differences were not statistically significant in the BNSTld, PVN or VMH in any of the exposed groups. No effect of exposure was found in females.

 
this study demonstrates that prenatal BPA exposure disrupts PPI and decreases PV-positive neurons in the PFC of adult female rats. In other words, early neurodevelopment can be sex-specifically impaired by BPA, which may consequently increase susceptibility to schizophrenia in adulthood.

AI: 

 Recent data (2010–2021) indicates that masculinizing (FTM) procedures increased by over fourfold, while feminizing (MTF) procedures increased nearly sevenfold during the same period. There has been a general significant rise in the total number of gender-affirming surgeries performed annually, with some years showing nearly a tripling of total procedures.

No comments:

Post a Comment