Besides its potential roles as a central neuromodulator or a hypothalamic neurohormone, neurotensin (NT) may also have endocrine function in the anterior pituitary of mammals. We previously found that NT immunoreactivity is present in the secretory granules of gonadotropes and thyrotropes in both male and female rats, where its levels of expression are under the control of sex steroids. In this work, using immunocytochemistry and in situ hybridization, we have studied the postnatal development of NT-like immunoreactivity (NTir) and the mRNA encoding NT (mRNA-NT) in specific anterior pituitary cells of both male and female rats. NT expression starts after birth and displays an identical pattern in both sexes until sexual maturity, with mRNA-NT being detected from day 2 of postnatal life in thyrotropes localized in the central portion of the anterior lobe. This pattern of expression develops progressively throughout the 2nd and 3rd weeks in both sexes. By the beginning of the 3rd week, mRNA-NT can also be detected in gonadotropes localized in the periphery of the gland coinciding with a rise in serum estradiol concentrations in both sexes, and by day 21, mRNA-NT is extensively present in both the periphery and the central region. NTir is observed from days 5–6 in thyrotropes predominantly localized in the central portion of the anterior lobe, and by day 21, NTir is also detected in gonadotropes localized in the periphery of the gland. This pattern remains similar in both sexes until the time of puberty, when female rats start displaying plastic changes in NT expression according to the stage of the estrous cycle. These findings indicate that NT expression in the rat anterior pituitary is cell specific, and develops from birth to adulthood under the control of sex steroid hormones. In addition, preliminary data showing the presence of NT receptors in rat pituitary cells support the hypothesis of a paracrine or an autocrine role for this peptide within the pituitary.

The neuropeptide neurotensin (NTS) is involved in regulating the reproductive axis and is expressed at each level of this axis (hypothalamus–pituitary–gonads). This dependence on estrogen levels has been widely demonstrated in the hypothalamus and pituitary. We focused on confirming the relationship of NTS with estrogens and the gonadal axis, using a particularly important environmental estrogenic molecule, bisphenol-A (BPA). Based on the experimental models or in vitro cell studies, it has been shown that BPA can negatively affect reproductive function. We studied for the first time the action of an exogenous estrogenic substance on the expression of NTS and estrogen receptors in the pituitary-gonadal axis during prolonged in vivo exposure. The exposure to BPA at 0.5 and 2 mg/kg body weight per day during gestation and lactation was monitored through indirect immunohistochemical procedures applied to the pituitary and ovary sections. Our results demonstrate that BPA induces alterations in the reproductive axis of the offspring, mainly after the first postnatal week. The rat pups exposed to BPA exhibited accelerated sexual maturation to puberty. There was no effect on the number of rats born per litter, although the fewer primordial follicles suggest a shorter fertile life.

With the aim of studying delta‐like protein 1 (DLK1) with respect to the relationship between adipocyte leptin and adenohypophyseal hormones, we carried out an immunohistochemical study analysing the presence of receptors for these hormones in the pituitary and adipose cells of male wild‐type (WT) mice (Dlk1^+/+) compared to knockout (KO) mice (Dlk1^−/−). ThemRNAexpression of these molecules was also determined using the reverse transcriptase‐polymerase chain reaction. The results obtained showed that, in WT adipose cells, all of the adenohypophyseal hormone receptors were present, with a highermRNAexpression for growth hormone (GH) receptorand thyroid‐stimulating hormone (TSH) receptor. Of the total cells in the anterior pituitary lobe, 17.09±0.9% were leptin receptor (LEPR) immunoreactive (‐IR), mainly inGH‐IR and prolactin (PRL)‐IR cells (41.5±3.8%; 13.5±1.7%, respectively). InDlk1^−/−mice, adipocyte cells showed a significant increase in theTSH receptor mRNAexpression level. Moreover, the percentage ofLEPR‐IRGHcells showed a statistically significant increase compared to controls, from 41.5±3.8% to 53.1±4.0%. By contrast, only 3.0±0.6% ofLEP‐IR anterior pituitary cells were detected in Dlk1 KO mice, as opposed to 6.8±1.1% observed inWTmice. The results suggest that relationships exist between adipocytes and pituitaryGH,PRLandTSHcells, in addition to an influence with respect to the synthesis and release of pituitary leptin, particularly inPRLcells.

The paraventricular nucleus (PVN) plays a central role in neuroendocrine and autonomic regulation, including male sexual behaviour. Dopaminergic and nitrergic signalling within the PVN are functionally linked, but their cellular relationship remains unclear. We examined the colocalization of dopamine D1 and D2 receptors with neuronal nitric oxide synthase (nNOS) in adult male rats using double‐label immunohistochemistry. nNOS‐immunoreactive neurons were widely distributed in PVN, with subsets co‐expressing D1R or D2R. Approximately 45% of nNOS‐positive neurons expressed dopaminergic receptors. These findings provide structural evidence for dopaminergic–nitrergic interaction in the PVN and support the possibility of direct dopaminergic modulation of nitrergic neurons.

Uterine leiomyosarcoma (LMS) is a rare and aggressive malignancy with diagnostic challenges, particularly in cases with overlapping histological features with atypical leiomyoma or smooth muscle tumors of uncertain malignant potential. We report a comparative immunohistochemical analysis of LMS, leiomyoma, and adjacent myometrium obtained from a 40-year-old woman with discordant pathological diagnoses. LMS tissue showed increased Ki67 and NTS/NTSR1 immunoreactivity together with a distinctive cytoplasmic localization of estrogen receptor beta (ERβ), in contrast to the predominantly nuclear localization observed in leiomyoma and normal myometrium. Importantly, focal areas within adjacent morphologically non-neoplastic myometrium exhibited an immunophenotype resembling LMS, including cytoplasmic ERβ localization and increased Ki67 and NTS/NTSR1 expression. These observations suggest a potential association between ERβ subcellular localization, NTS/NTSR1 signaling, and molecular alterations occurring during uterine smooth muscle tumorigenesis. However, given the single-case nature of this report, these findings should be considered exploratory and require validation in larger studies. The diagnostic message conveyed by these images may assist in the interpretation of diagnostically challenging cases and provide a basis for future investigation.