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Distribution and Characteristics of Brain Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
The human pituitary gland is a size of a pea and weighs ~500 mg, while the rat pituitary gland weighs 12–15 mg. The pituitary consists of two lobes, anterior and posterior that arise from distinct parts of embryonic tissue. The posterior pituitary (PP) or neural lobe (NL) has its embryological origin in nervous tissue, given that it develops from a down-growth of the diencephalon that forms the floor of the third ventricle. On the other hand, the anterior lobe (AL), also called the pars distalis or anterior pituitary (AP), is derived from an up-growth of the oral ectoderm within the primitive oral cavity, called the Rathke’s pouch (Figure 3.10). The pituitary organogenesis is a highly complex and tightly regulated process that depends on several transcription factors such as PROP1, PIT1 (POU1F1), HESX1, LHX3, and LHX4 [39]. Mutations in these genes can result in different combinations of hypopituitarism that can be associated with structural alterations of the CNS, causing the congenital form of panhypopituitarism. Detailed information of the cellular composition and hormone synthesis and regulation by the pituitary gland is presented in Chapter 5.
Scientific Basis of Male Hypogonadism
Published in Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George, The Scientific Basis of Urology, 2010
Thang S. Han, Pierre-Marc G. Bouloux
The pituitary transcription factor-1 (PIT-1) and prophet of PIT-1 (PROP1) play an important role in the ontogenesis, differentiation, and function of somatotrophic, lactotrophic, thyrotrophic and gonadotrophic cells. Mutations in these factors result in pituitary hormone deficiencies (gonadotrophins, growth hormone, prolactin, and TSH) and delayed puberty and hypogonadism (29). Other factors that regulate pituitary differentiation include LHX3, a homeodomain transcription factor, and HESX-1 gene expressed in embryonic brain and pituitary. Mutations of HESX-1, a transcription factor and homeobox gene, cause septo-optic dysplasia (30), a syndrome characterized by panhypopituitarism, optic nerve atrophy, and midline defects of the cerebrum (corpus callosum agenesis). Another genetic cause of pituitary failure is due to inactivating mutations of LH β-chain, which results in LH deficiency and thus androgen deficiency and infertility.
Regenerative replacement of neural cells for treatment of spinal cord injury
Published in Expert Opinion on Biological Therapy, 2021
William Brett McIntyre, Katarzyna Pieczonka, Mohamad Khazaei, Michael G. Fehlings
A population of propriospinal INs that has gained interest for cell replacement therapy for SCI belong to the V2a subpopulation. V2a INs are crucial for the transmission and coordination of motor and sensory functions. V2a INs are identified by expression of the Hox10/Vsx2, Shox2, Lhx3, and Lhx4 transcription factors, but there is considerable diversity within V2a INs, with differentially expressed molecular markers corresponding to spatial location, projection targets, and timing physiological patterning ques [94,111–114]. Transplantation of V2a INs that can transmit signals propriospinally or interstitially could be helpful for restoring damaged ascending and descending circuits [111]. Recently, transplantation of Hox10+ V2a INs following SCI has promoted functional recovery [111].
Maternal obesity, diabetes during pregnancy and epigenetic mechanisms that influence the developmental origins of cardiometabolic disease in the offspring
Published in Critical Reviews in Clinical Laboratory Sciences, 2018
Prasoon Agarwal, Taylor S. Morriseau, Stephanie M. Kereliuk, Christine A. Doucette, Brandy A. Wicklow, Vernon W. Dolinsky
An epigenome-wide association study in the Pima Indian population reported differences in DNA methylation in the offspring (average age 12.9 years ±5.7) of mothers with T2D (n = 187; 77 males, 110 females; 23 were siblings, 178 were unrelated) compared to offspring (average age 13.0 ± 5.7) of mothers without diabetes during the pregnancy (n = 201; 82 males, 119 females; 69 were siblings, 118 were unrelated) [174]. These authors reported hypermethylation of several genes in the offspring of diabetic mothers, including Sbk1 and Prdm16 that are associated with a higher risk of diabetes, as well as Lhx3, which interacts with several transcription factors (e.g. Isl1 and Lmx1a) that are known regulators of insulin gene expression [175]. The sample size, availability of detailed clinical parameters, and longitudinal cohort were strengths of this study, although DNA methylation analyses were performed on individuals with a mean age of 13 years, so the changes in DNA methylation could also have been influenced by the postnatal environment. The next phase of research on epigenetic mechanisms in humans should use tissues from animal models or cadaveric sampling to delineate the concordance between epigenetic observations in human PBLs and metabolic tissues. This research would further benefit from large birth cohort studies with prospective measures of comprehensive domains of exposures and outcomes [156,176].
What are the pharmacological considerations for male congenital hypogonadotropic hypogonadism?
Published in Expert Opinion on Pharmacotherapy, 2022
Giulia Rastrelli, Mario Maggi, Giovanni Corona
Genes involved in CHH associated with other pituitary hormone deficiency (Congenital Combined Pituitary Hormone Deficiency; CPHD) overlap with isolated CHH because mutations in FGFR1, FGF8, and PROKR2 have been found in both forms [2]. Besides these, mutations in genes codifying for transcription factors involved in Rathke pouch development may cause congenital CPHD, including LHX3, LHX4, and PROP1 [2].