Age-related changes in sexual function and steroid-hormone receptors in the medial preoptic area of male rats

Abstract

Testosterone is the main circulating steroid hormone in males, and acts to facilitate sexual behavior via both reduction to dihydrotestosterone (DHT) and aromatization to estradiol. The mPOA is a key site involved in mediating actions of androgens and estrogens in the control of masculine sexual behavior, but the respective roles of these hormones is not fully understood. As males age they show impairments in sexual function, and a decreased facilitation of behavior by steroid hormones compared to younger animals. We hypothesized that an anatomical substrate for these behavioral changes is a decline in expression and/or activation of hormone receptor-sensitive cells in the mPOA. We tested this by quantifying and comparing numbers of AR- and ERα-containing cells, and Fos as a marker of activated neurons, in the mPOA of mature (4-5 months) and aged (12-13 months) male rats, assessed one hour after copulation to one ejaculation. Numbers of AR- and ERα cells did not change with age or after sex, but the percentage of AR- and ERα-cells that co-expressed Fos were significantly up-regulated by sex, independent of age. Age effects were found for the percentage of Fos cells that co-expressed ERα (up-regulated in the central mPOA) and the percentage of Fos cells co-expressing AR in the posterior mPOA. Interestingly, serum estradiol concentrations positively correlated with intromission latency in aged but not mature animals. These data show that the aging male brain continues to have high expression and activation of both AR and ERα in the mPOA with copulation, raises the possibility that differences in relationships between hormones, behavior, and neural activation may underlie some age-related impairments.

The timing and duration of estradiol treatment in a rat model of the perimenopause: Influences on social behavior and the neuromolecular phenotype

“…In the MeA, the most genes were affected (11), nearly all with a unique expression pattern, showing the various effects of E 2 presence or absence, timing, and duration. It is also worth noting that in a separate study on effects of E 2 in the brain of young adult vs. aging male rats (Nutsch et al, 2017), we conducted a similar 48-gene qPCR analysis in 3 regions [preoptic area, BnST, and MeA (posterodorsal subdivision)]. Results showed that by far, the MeA was most sensitive to age/E 2 treatment in males – similar to our current finding in the female MeA.…”

Understanding and treating ejaculatory dysfunction in men with diabetes mellitus

“…99 Of pertinence to this review is the knowledge that androgen receptors (AR) are expressed at various sites involved in the ejaculation process, both peripheral and central. For example, AR are located at the MPOA 100 and PVN 101 of the hypothalamus, in the spinal nuclei of motor nerves supplying bulbocavernosus 102 and the smooth muscle lining the seminal tract. 103 Nevertheless, there is less robust evidence explaining the direct role of T in EjD than the peripheral neuropathy seen in DM.…”

Ejaculatory dysfunction in men with diabetes mellitus

“…However, it has been shown that testosterone supplement is not able to bring back ejaculatory function in induced diabetic rats[ 46 , 77 ] suggesting that the deficiency of testosterone was not related directly to the diabetes-induced ejaculatory dysfunction in this experimental model. Although expression of androgen receptors are demonstrated at different levels of the ejaculatory process such as the medial preoptic area of the hypothalamus[ 78 ], smooth muscles of the male genital tract[ 79 ], and in the spinal nucleus of the bulbocavernosus muscle[ 80 ], it is thought that testosterone plays a much superior role in libido than the ejaculatory process and the physiological capacity for ejaculation is less sensitive to testosterone reduction than that for the desire[ 81 , 82 ]. In support of this notion, it has been shown that testosterone levels as low as 0.2 ng/mL, can support ejaculatory behavior in rats[ 83 ]; (8) It is possible that diabetic ejaculatory dysfunction might be a reflection of decreased sexual desire[ 36 , 48 ].…”