Age and Long-Term Hormone Treatment Effects on the Ultrastructural Morphology of the Median Eminence of Female Rhesus Macaques

Naugle, Michelle M.; Lozano, Sateria A.; Guarraci, Fay A.; Lindsey, Larry; Kim, Ji E.; Morrison, John H.; Janssen, William G.M.; Yin, Wang; Gore, Andrea C.

doi:10.1159/000442015

Cited by 11 publications

(8 citation statements)

References 76 publications

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“…Overall, however, the data from the present study show that gene expression in the ARC of male rhesus macaques is largely resistant to aging, especially genes that are associated with the neuroendocrine reproductive axis. Furthermore, the results largely agree with recent observations made in female rhesus macaques showing that the overall cytoarchitecture and sex-steroid receptor expression in the hypothalamus undergo relatively few changes with age and hormone supplementation (Naugle et al 2014; 2016). …”

Section: Discussionsupporting

confidence: 91%

Age-associated gene expression changes in the arcuate nucleus of male rhesus macaques

Eghlidi

Garyfallou

Kohama

et al. 2017

Journal of Molecular Endocrinology

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The hypothalamic arcuate nucleus (ARC) represents a major component of the neuroendocrine reproductive axis, and plays an important role in controlling the onset of puberty as well as age-associated reproductive senescence. Although significant gene expression changes have been observed in the ARC during sexual maturation it is unclear what changes occur during aging, especially in males. Therefore, in the present study we profiled the expression of reproduction-related genes in the ARC of young and old male rhesus macaques, as well as old males that had received 6 months of hormone supplementation (HS) in the form of daily testosterone and dehydroepiandrosterone; we also compared morning versus night ARC gene expression in the old males. Using Affymetrix gene microarrays, we found little evidence for age-associated expression changes for genes associated with the neuroendocrine reproductive axis, whereas using qRT-PCR we detected a similar age-associated decrease in PGR (progesterone receptor) that we previously observed in post-menopausal females. We also detected a sex-steroid-dependent and age-associated decrease in AR (androgen receptor) expression, with highest AR levels being expressed at night (i.e., coinciding with the natural peak in daily testosterone secretion. Finally, unlike previous observations made in females, we did not find a significant age-associated increase in KISS1 (Kisspeptin) or TAC3 (Neurokinin B) expression in the ARC of males, most likely because the attenuation of circulating sex-steroid levels in the males was much less than that in postmenopausal females. Taken together, the data highlight some similarities and differences in ARC gene expression between aged male and female nonhuman primates.

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Section: Discussionsupporting

confidence: 91%

Age-associated gene expression changes in the arcuate nucleus of male rhesus macaques

Eghlidi

Garyfallou

Kohama

et al. 2017

Journal of Molecular Endocrinology

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“…There are reports of high oestrogen sensitivity and morphological changes in nerve endings in the ME due to aging 9 . During reproductive aging, the ME may play physiological roles because of the high oestrogen sensitivity of this region and the ability of E2 to induce dynamic morphological changes in nerve terminals and glial cells 18 , 26 .…”

Section: Discussionmentioning

confidence: 99%

“…Previously, the morphological organisation and significant changes in cell structure of aging rat ME were reported, but short-term E2 treatment had little effect 27 . In monkeys, age-related and E2-related changes were found in the expression of genes encoding kisspeptin, neurokinin B, and prozinorphin ( KISS1 , NKB , and PDYN ) in a combined dissection of the arcuate nucleus and the ME 9 , 28 . In our study, we examined the influence of AVP only in the eME (no AVP confirmation in the iME), but we confirmed the presence of AVP granules in the eME domain.…”

Section: Discussionmentioning

confidence: 99%

“…In order to communicate from the pituitary portal vein to the anterior pituitary gland, the eME also has the role of regulating the secretion of the anterior pituitary hormone. There are reports of age and long-term hormone treatment effects on the ultrastructural morphology of the ME 9 . The effect of sex differences and the oestrus cycle remains unknown, although several studies showed that AVP in the i/eME fluctuates after water deprivation 10 , salt loading 11 , and high-stress conditions 12 .…”

Section: Introductionmentioning

confidence: 99%

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Effect of oestrogen-dependent vasopressin on HPA axis in the median eminence of female rats

Nishimura

Yoshino

Sanada

et al. 2019

Sci Rep

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The median eminence (ME) anatomically consists of external (eME) and internal (iME) layers. The hypothalamic neurosecretory cells terminate their axons in the eME and secrete their neurohormones regulating anterior pituitary hormone secretion involved in stress responses into the portal vein located in the eME. Magnocellular neurosecretory cells (MNCs) which produce arginine vasopressin (AVP) and oxytocin in the paraventricular (PVN) and supraoptic nuclei (SON) terminate their axons in the posterior pituitary gland (PP) through the iME. Here, we provide the first evidence that oestrogen modulates the dynamic changes in AVP levels in the eME axon terminals in female rats, using AVP-eGFP and AVP-DREADDs transgenic rats. Strong AVP-eGFP fluorescence in the eME was observed at all oestrus cycle stages in adult female rats but not in male transgenic rats. AVP-eGFP fluorescence in the eME was depleted after bilateral ovariectomy but re-appeared with high-dose 17β-oestradiol. AVP-eGFP fluorescence in the MNCs and PP did not change significantly in most treatments. Peripheral clozapine-N-oxide administration induced AVP-DREADDs neurone activation, causing a significant increase in plasma corticosterone levels in the transgenic rats. These results suggest that stress-induced activation of the hypothalamic-pituitary-adrenal axis may be caused by oestrogen-dependent upregulation of AVP in the eME of female rats.

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“…We also used an anti-GnRH mouse monoclonal antibody (clone number GnRH I HU11B: sc-32292, Santa Cruz Biotechnology, Inc., Dallas, TX, USA) raised against a synthetic GnRH I decapeptide by Urbanski (1991) [27]. This antibody was used for immunohistochemistry to visualize GnRH neurons in rat and monkey [28,29].…”

Section: Antibodies Used In This Studymentioning

confidence: 99%

Anti-Müllerian hormone and its receptor are detected in most gonadotropin-releasing-hormone cell bodies and fibers in heifer brains

Kereilwe

Kadokawa

2020

Domestic Animal Endocrinology

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Circulating concentrations of Anti-Müllerian hormone (AMH) can indicate fertility in various animals, but the physiological mechanisms underlying the effect of AMH on fertility remain unknown. We recently discovered that AMH has extragonadal functions via its main receptor, AMH receptor type 2 (AMHR2). Specifically, AMH stimulates the secretion of luteinizing hormone and follicle stimulating hormone from bovine gonadotrophs. Moreover, gonadotrophs themselves express AMH to exert paracrine/autocrine functions, and AMH can activate gonadotropin-releasing-hormone (GnRH) neurons in mice. This study aimed to evaluate whether AMH and AMHR2 are detected in areas of the brain relevant to neuroendocrine control of reproduction: the preoptic area (POA), arcuate nucleus (ARC), and median eminence (ME), and in particular within GnRH neurons. Reverse transcription-polymerase chain reaction detected both AMH and AMHR2 mRNA in tissues containing POA as well as in those containing both ARC and ME, collected from post-pubertal heifers. Western blotting detected AMH and AMHR2 protein in the collected tissues. Triple fluorescence immunohistochemistry revealed that the majority of cell bodies or fibers of GnRH neurons were AMHR2-positive and AMH-positive, although some were negative.Immunohistochemistry revealed that 75 to 85% of cell bodies and fibers of GnRH neurons were positive for both AMH and AMHR2 in the POA, ARC, and both the internal and external zones of ME. The cell bodies of GnRH neurons were situated around other AMHpositive cell bodies or fibers of GnRH and non-GNRH neurons. Our findings thus indicate that AMH and AMHR2 are detected in the majority of cell bodies or fibers of GnRH neurons in POA, ARC, or ME of heifer brains. These data support the need for further study as to how AMH and AMHR2 act within the hypothalamus to influence GnRH and gonadotropin secretion.

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Age and Long-Term Hormone Treatment Effects on the Ultrastructural Morphology of the Median Eminence of Female Rhesus Macaques

Cited by 11 publications

References 76 publications

Age-associated gene expression changes in the arcuate nucleus of male rhesus macaques

Age-associated gene expression changes in the arcuate nucleus of male rhesus macaques

Effect of oestrogen-dependent vasopressin on HPA axis in the median eminence of female rats

Anti-Müllerian hormone and its receptor are detected in most gonadotropin-releasing-hormone cell bodies and fibers in heifer brains

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