Manuel Carretero

Local transformations of androgens into estradiol by aromatase P450 is involved in the regulation of prolactin and the proliferation of pituitary prolactin-positive cells.

In previous studies we demonstrated the immunohistochemical expression of aromatase in pituitary cells. In order to determine whether pituitary aromatase is involved in the paracrine regulation of prolactin-producing pituitary cells and the physiological relevance of pituitary aromatase in the control of these cells, an in vivo and in vitro immunocytochemical and morphometric study of prolactin-positive pituitary cells was carried out on the pituitary glands of adult male rats treated with the aromatase antagonist fadrozole. Moreover, we analyzed the expression of mRNA for the enzyme in pituitary cells of male adult rats by in situ hybridization. The aromatase-mRNA was seen to be located in the cytoplasm of 41% of pituitary cells and was well correlated with the immunocytochemical staining. After in vivo treatment with fadrozole, the size (cellular and nuclear areas) of prolactin cells, as well as the percentage of prolactin-positive cells and the percentage of proliferating-prolactin cells, was significantly decreased. Moreover, fadrozole decreased serum prolactin levels. In vitro, treatment with fadrozole plus testosterone induced similar effects on prolactin-positive cells, inhibiting their cellular proliferation. Our results suggest that under physiological conditions aromatase P450 exerts a relevant control over male pituitary prolactin-cells, probably transforming testosterone to estradiol in the pituitary gland.

The expression of AIB1 correlates with cellular proliferation in human prolactinomas.

Estrogens as well as certain growth factors strongly influence the development and growth of prolactinomas. However, the molecular mechanisms by which extracellular factors trigger prolactinomas are not well known. Amplified in breast cancer 1 (AIB1), also known as steroid receptor co-activator 3 (SRC-3), belongs to the p160/SRC family of nuclear receptor co-activators and is a major co-activator of the estrogen receptor. Here, we report that the estrogen receptor coactivator AIB1 is overexpressed in human prolactinomas and correlates with the detection of aromatase and estrogen receptor α (ERα). Of the 87 pituitary tumors evaluated in women, 56%, corresponding to hyperoprolactinemic women, contained an enriched population of prolactin-positive cells and hence were further classified as prolactinomas. All prolactinomas stained positive for both ERα and AIB1. Moreover, AIB1 sub-cellular distribution was indicative of the cell-cycle status of tumors; the nuclear expression of AIB1 was correlated with proliferative markers whereas the cytoplasmic localization of AIB1 coincided with active caspase-3. Thus, our results demonstrate for the first time that AIB1 is expressed in prolactinomas and suggest its participation in the regulation of proliferation and apoptosis of tumoral cells. Because aromatase expression is also enhanced in these prolactinomas and it is involved in the local production of estradiol, both mechanisms, ER-AIB1 and aromatase could be related.

Endothelial immunocytochemical expression of pituitary IL-1β and its relation to ACTH-positive cells is regulated by corticosterone in the male rat

HighlightsWe analyzed the relationship among the pituitary cells expressing IL‐1&bgr; and ACTH.Immunocytochemical expression of both polypeptides was studied in stress situations.IL‐1&bgr; was located in pituitary endothelial cells at the hypophyseal portal vessels.Pituitary endothelial expression of IL‐1&bgr; was independent of the treatment.Endothelial pituitary IL‐1&bgr; could regulate ACTH in a paracrine fashion. Abstract Interleukin‐1 beta (IL‐1&bgr;) is a cytokine linking the neuroendocrine system and metabolic homeostasis. We have previously demonstrated the relevance of IL‐1&bgr; for maintaining the pituitary ACTH‐producing cells by immuno‐blocking its effects in pituitary cultures. However, the morphological characteristics and the intimate relationship of the pituitary cells expressing IL‐1&bgr; and ACTH remain unknown. For determining pituitary variations of immunoreactivity for IL‐1&bgr; and its relation with ACTH‐positive cells under stress situations, we performed an immunohistochemical analysis of the expression of IL‐1&bgr; and ACTH in the pituitary gland of adult rats, in the absence or presence of corticosterone, by establishing different groups: untreated, sham‐operated, and bilaterally adrenalectomized animals. In the rats subjected to surgery, the glucocorticoid was administered on the same day of the intervention and on the third day post‐surgery. Interestingly, it was observed that IL‐1&bgr; was located in the pituitary endothelial cells at the hypophyseal portal vessels, regardless of the treatment schedule. When comparing the pituitary immunoreactive surface to IL‐1&bgr; expression without corticosterone, adrenalectomized animals displayed a significantly greater area than the sham‐operated animals. Corticosterone significantly inhibited the effect of adrenalectomy depending on the time interval it was administered. By in situ hybridization, IL‐1&bgr; mRNA expression was also correlated with immnunocytochemical expression of pituitary IL‐1&bgr;. Our results demonstrate that IL‐1&bgr; is a constitutive element in endothelial portal pituitary vessels and under stress experimental conditions IL‐1&bgr; increases its expression and its relation with ACTH‐positive cells, suggesting that IL‐1&bgr; could participate in an autocrine‐paracrine fashion thereby modulating the pituitary population of ACTH‐positive cells.

Specific Changes in Young Soccer Player's Fitness After Traditional Bilateral vs. Unilateral Combined Strength and Plyometric Training

The aim of this study was to compare changes in young soccer players fitness after traditional bilateral vs. unilateral combined plyometric and strength training. Male athletes were randomly divided in two groups; both received the same training, including strength training for knee extensors and flexors, in addition to horizontal plyometric training drills. The only difference between groups was the mode of drills technique: unilateral (UG; n = 9; age, 17.3 ± 1.1 years) vs. bilateral (TG; n = 9; age, 17.6 ± 0.5 years). One repetition maximum bilateral strength of knee muscle extensors (1RM_KE) and flexors (1RM_KF), change of direction ability (COD), horizontal and vertical jump ability with one (unilateral) and two (bilateral) legs, and limb symmetry index were measured before and after an 8-week in-season intervention period. Some regular soccer drills were replaced by combination of plyometric and strength training drills. Magnitude-based inference statistics were used for between-group and within-group comparisons. Beneficial effects (p < 0.05) in 1RM_KE, COD, and several test of jumping performance were found in both groups in comparison to pre-test values. The limb symmetry index was not affected in either group. The beneficial changes in 1RM_KE (8.1%; p = 0.074) and 1RM_KF (6.7%; p = 0.004), COD (3.1%; p = 0.149), and bilateral jump performance (from 2.7% [p = 0.535] to 10.5% [p = 0.002]) were possible to most likely beneficial in the TG than in the UG. However, unilateral jump performance measures achieved likely to most likely beneficial changes in the UG compared to the TG (from 4.5% [p = 0.090] to 8.6% [p = 0.018]). The improvements in jumping ability were specific to the type of jump performed, with greater improvements in unilateral jump performance in the UG and bilateral jump performance in the TG. Therefore, bilateral strength and plyometric training should be complemented with unilateral drills, in order to maximize adaptations.

Relation among Aromatase P450 and Tumoral Growth in Human Prolactinomas

The pituitary gland is part of hypothalamic-pituitary–gonadal axis, which controls development, reproduction, and aging in humans and animals. In addition, the pituitary gland is regulated mainly by hormones and neurotransmitters released from the hypothalamus and by systemic hormones secreted by target glands. Aromatase P450, the enzyme responsible for the catabolization of aromatizable androgens to estrogens, is expressed in different parts of body, including the pituitary gland. Moreover, aromatase P450 is involved in sexual dimorphism where alteration in the level of aromatase can initiate a number of diseases in both genders. On the other hand, the direct actions of estrogens, mainly estradiol, are well known for stimulating prolactin release. Numerous studies have shown that changes in the levels of estrogens, among other factors, have been implicated in the genesis and development of prolactinoma. The pituitary gland can produce estradiol locally in several types of endocrine cells, and it is possible that aromatase could be responsible for the maintenance of the population of lactotroph cells and the modulation of the action of central or peripheral regulators. Aromatase overexpression due to inappropriate gene regulation has clinical effects such as the pathogenesis of prolactinomas. The present study reports on the synthesis of pituitary aromatase, its regulation by gonadal steroids, and the physiological roles of aromatase on pituitary endocrine cells. The involvement of aromatase in the pathogenesis of pituitary tumors, mainly prolactinomas, through the auto-paracrine production of estradiol is reviewed.

Soccer Small-Sided Games Activities Vary According to the Interval Regime and their Order of Presentation within the Session

Abstract In order to investigate the physical demands of widely used in soccer small-sided games (SSGs), we compared game variations performed under different interval (fixed or variable) and timing regimens (beginning or end of a training session). Twelve male players wore GPS devices during the SSGs to record total distance, relative distance, distance at different speeds, and maximum velocity variables. Four variations of SSGs (4x4) were randomly applied: beginning of a training session with fixed and variable recovery, or end of a training session with fixed and variable recovery. During the beginning or end of a training session settings with fixed recovery duration, 2-min of playing and 2-min of recovery were provided. During the beginning and end of a training session settings with variable recovery, athletes kept playing until a goal was scored, or up to 2-min if no goals were scored. Results were analysed using MANOVA. Total distance and relative distance were higher in the beginning compared to end of training sessions for both fixed and variable recovery duration (small to moderate effect sizes). Distance at various speed ranges (i.e., 13-18 km/h and >18 km/h) was higher (p ≤ 0.01) at the beginning than at the end of training sessions with variable recovery. In addition, distance >18 km/h was higher at the beginning of a training session with variable recovery than fixed recovery and at the end of a training session with variable recovery than fixed recovery. In conclusion, several physical demand characteristics are affected by the moment of SSG application, while others respond to the recovery regime during SSGs, thus providing indications to the coaches to prescribe the intended training intensity by manipulating the context.