Abstract
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 −/−). The mRNA expression 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 higher mRNA expression for growth hormone (GH) receptor and 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 in GH‐IR and prolactin (PRL)‐IR cells (41.5±3.8%; 13.5±1.7%, respectively). In Dlk1 −/− mice, adipocyte cells showed a significant increase in the TSH receptor mRNA expression level. Moreover, the percentage of LEPR‐IR GH cells 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% of LEP‐IR anterior pituitary cells were detected in Dlk1 KO mice, as opposed to 6.8±1.1% observed in WT mice. The results suggest that relationships exist between adipocytes and pituitary GH, PRL and TSH cells, in addition to an influence with respect to the synthesis and release of pituitary leptin, particularly in PRL cells.
Highlights
At present, white adipose tissue is known to be an active endocrine organ producing hormones such as leptin (LEP), proinflammatory and anti-inflammatory cytokines, and numerous other regulatory factors.[1,2] In 1994, adipose tissue was shown to produce the hormone LEP, with the Ob gene being discovered in mice for the first time.[3]
The data indicated that the receptors with the highest RNA expression were Growth hormone receptor (GHR) and TSHR, followed by Adrenocorticotrophic hormone receptor (ACTHR), whereas Prolactin hormone receptor (PRLR), Luteinising hormone receptor (LHR) and Follicle-stimulating hormone receptor (FSHR) had a lower level (Figure 2)
In adipocytes from Dlk1−/− mice, the presence of immunoreactive cells was detectable for all antibodies used against adenohypophyseal hormone receptors (ACTHR, TSHR, FSHR, LHR, PRLR and GHR)
Summary
White adipose tissue is known to be an active endocrine organ producing hormones such as leptin (LEP), proinflammatory and anti-inflammatory cytokines, and numerous other regulatory factors.[1,2] In 1994, adipose tissue was shown to produce the hormone LEP, with the Ob gene being discovered in mice for the first time.[3]. Regarding the regulation of adipocyte LEP production, delta-like protein 1 (DLK1) is a transmembrane protein with regulatory effects on adipocyte differentiation.[26,27,28] Dlk[1] mRNA is widely expressed during embryonic development, in the adult, Dlk[1] mRNA expression is limited to some endocrine glands and subsets of neurones in the brain, including the hypothalamus.[29,30,31,32] In the pituitary gland of the 129/Svj wild-type (WT) mouse, we previously demonstrated that DLK1 is expressed in all types of cells, in somatotroph cells.[33,34] we used a Dlk[1] knockout (KO) mouse of the same strain that displays a smaller pre-and postnatal size but increased white fat mass in the adult.[35,36] The results obtained showed increased serum leptin in these KO mice, as well as a slight increase in GH levels, despite having a smaller number of GH-producing cells.[33] Based on these data, the present study aimed to investigate in situ (ie, maintaining the natural context of the cells), the influence of DLK1 protein on the relationship between adipocyte and adenohypophyseal cells, using male WT and Dlk1−/− KO mice of the strain 129/SvJ
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