Ginseng in Hair Growth and Viability

The hair follicle is the unique organ that has the capacity of undergoing cyclic transformations following periods of growth (anagen), regression (catagen), and rest (telogen) regenerating itself to restart the cycle. The dynamic capacity of hair to growth and rest enables mammals to control hair growth and length in different body side and to change their coats. Unlike what is observed in many animals in which the pelage synchronously passes from one phase of the cycle to other all stages of growth cycle are simultaneously found in the human pelage, the growth pattern is a mosaic where the hair cycling staging of one hair root is completely independent of it nearest hair follicle, meaning that each follicular unit (FU) can contain follicles in different stages at any given time. A variety of factors, such as nutritional status, hormones, exposure to radiations, chemotherapy or radiotherapy, environmental pollution or drugs may affect hair growth, and affects the number of hairs, this progressive hair loss has a cosmetic and social impact that often significantly affects social and psychological well-being of the patient that suffers from this hair loss. Although a number of therapies, such as finasteride and minoxidil, are approved medications, a wide variety of classes of phytochemicals and natural products, including those present in ginseng are being testing. The purpose of this chapter is to focus on study the potential of ginseng and its metabolites in hair loss

Influence of Neonatal Hypothyroidism on Hepatic Gene Expression and Lipid Metabolism in Adulthood

Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology, but its specific influence in liver is less understood. Here, we studied how CH influences the liver gene expression program in adulthood. Pregnant rats were given the antithyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as reductions in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, the feed efficiency increased in CH, and this was accompanied by significant catch-up growth. On PND80, significant reductions in body mass, tail length, and circulating IGF-I levels remained in CH rats. Conversely, the mRNA levels of known GH target genes were significantly upregulated. The serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in the expression of hepatic genes involved in lipid metabolism, including an increased transcription of PPARα and a reduced expression of genes involved in fatty acid and cholesterol uptake, cellular sterol efflux, triglyceride assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to the onset of hypothyroidism in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters and to T3 replacement with an enhanced activation of malic enzyme. In summary, we provide in vivo evidence that neonatal hypothyroidism influences the hepatic transcriptional program and tissue sensitivity to hormone treatment in adulthood. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood

Effects of congenital hypothyroidism on mRNA expression levels of INSIG-1, SREBP2, LXR, and genes involved in lipid transport in adult rat liver.

<p>On PND80, the hepatic mRNA levels of INSIG1 (A), SREBP2 (B), LDLR (C), CD36 (D), ABCA (E), LXR (F), HLipase (G), HMGCoAS (H), and HMHCoAR (I) were measured by qPCR in CH, age-matched INTACT or weight-paired (WP) control groups. The mean mRNA expression level of each gene in the INTACT group is defined as 1, with all other expression values reported relative to this level. Bars represent mean ± SD from at least five individual animals. *, <i>P</i><0.05; ***, <i>P</i><0.001 for comparison with INTACT group. <b>+</b>, <i>P</i><0.05; <b>++</b>, <i>P</i><0.01; <b>+++</b>, <i>P</i><0.001 for comparison with WP group.</p

Effects of neonatal hypothyroidism on mRNA expression levels of IGF-I and IGFBP genes in adult rat liver.

<p>On PND80, the hepatic mRNA levels of IGF-I (A), IGFBP3 (B), and IGFBP2 (C) were measured by qPCR in rats exposed to neonatal hypothyroidism (CH), age-matched (INTACT) or weight-paired (WP) control groups. The mean mRNA expression level of each gene in the INTACT group is defined as 1, with all other expression values reported relative to this level. Bars represent mean ± SD from at least six individual animals. ***, <i>P</i><0.001 for comparison with INTACT group. <b>+++</b>, <i>P</i><0.001 for comparison with WP group.</p

Hepatic lipids in liver from PND80 male rats at baseline (INTACT), without (−CH) or with (+CH) transient neonatal exposure to MMI, during thyroid hormone deprivation (vehicle) and hormonal replacement.

<p> <b>INTACT and CH animals were exposed to MMI at PND60 as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037386#s2" target="_blank">Materials and Methods</a>. From day 73, animals were injected daily with vehicle, T3 or GH for 7 d. The animals were sacrificed on PND80 and hepatic lipids were measured. Results are expressed as mean ± SD (n = 6). Statistical comparison was performed for treated animals using INTACT animals or vehicle as controls.</b></p>*<p> <b>, </b><b><i>P</i></b><b><0.05;</b></p>**<p> <b>, </b><b><i>P</i></b><b><0.01;</b></p>***<p> <b>, </b><b><i>P</i></b><b><0.001 for comparison with INTACT rats;</b></p>+<p> <b>, </b><b><i>P</i></b><b><0.05;</b></p>++<p> <b>, </b><b><i>P</i></b><b><0.01 for comparison with vehicle.</b></p

Effects of neonatal hypothyroidism on mRNA expression levels of SOCS/CIS and male predominant genes in adult rat liver.

<p>On PND80, the hepatic mRNA levels of SOCS2 (A), CIS (B), SOCS3 (C), PIAS3 (D), SOCS5 (E), CYP2C11 (F), CYP2C13 (G) and CYP2C7 (H) were measured by qPCR in rats exposed to neonatal hypothyroidism (CH), age-matched (INTACT) or weight-paired (WP) control groups. The mean mRNA expression level of each gene in the INTACT group is defined as 1, with all other expression values reported relative to this level. Bars represent mean ± SD from at least six individual animals. ***, <i>P</i><0.001 for comparison with INTACT group. <b>++</b>, <i>P</i><0.01; <b>+++</b>, <i>P</i><0.001 for comparison with WP group.</p

Lipid Profiling and Transcriptomic Analysis Reveals a Functional Interplay between Estradiol and Growth Hormone in Liver

<div><p>17β-estradiol (E2) may interfere with endocrine, metabolic, and gender-differentiated functions in liver in both females and males. Indirect mechanisms play a crucial role because of the E2 influence on the pituitary GH secretion and the GHR-JAK2-STAT5 signaling pathway in the target tissues. E2, through its interaction with the estrogen receptor, exerts direct effects on liver. Hypothyroidism also affects endocrine and metabolic functions of the liver, rendering a metabolic phenotype with features that mimic deficiencies in E2 or GH. In this work, we combined the lipid and transcriptomic analysis to obtain comprehensive information on the molecular mechanisms of E2 effects, alone and in combination with GH, to regulate liver functions in males. We used the adult hypothyroid-orchidectomized rat model to minimize the influence of internal hormones on E2 treatment and to explore its role in male-differentiated functions. E2 influenced genes involved in metabolism of lipids and endo-xenobiotics, and the GH-regulated endocrine, metabolic, immune, and male-specific responses. E2 induced a female-pattern of gene expression and inhibited GH-regulated STAT5b targeted genes. E2 did not prevent the inhibitory effects of GH on urea and amino acid metabolism-related genes. The combination of E2 and GH decreased transcriptional immune responses. E2 decreased the hepatic content of saturated fatty acids and induced a transcriptional program that seems to be mediated by the activation of PPARα. In contrast, GH inhibited fatty acid oxidation. Both E2 and GH replacements reduced hepatic CHO levels and increased the formation of cholesterol esters and triacylglycerols. Notably, the hepatic lipid profiles were endowed with singular fingerprints that may be used to segregate the effects of different hormonal replacements. In summary, we provide <i>in vivo</i> evidence that E2 has a significant impact on lipid content and transcriptome in male liver and that E2 exerts a marked influence on GH physiology, with implications in human therapy.</p></div

Effects of hormonal replacement on body weight and hepatic mRNA expression levels of IGF-I, ME, and FAS in adult hypothyroid rats without or with transient exposure to neonatal hypothyroidism.

<p>Four groups were studied: 1) age-matched rats (INTACT); 2) adult rats with neonatal hypothyroidism (CH); 3) hypothyroid adult rats without CH (TX/−CH); and 4) hypothyroid adult rats with CH (TX/+CH). During the last week of life, TX/−CH and TX/+CH groups were treated with either T3 or GH daily. Control animals were injected with saline (VEH). Body weight (A and B) as well as hepatic mRNA levels of IGF-I (C), ME (D) and FAS (E) were measured. The hepatic mRNA levels of TRα (F) and TRβ (G) were also measured by qPCR in CH, age-matched INTACT or weight-paired (WP) control groups. The mean mRNA expression level of each gene in the INTACT group is defined as 1, with all other expression values reported relative to this level. Results represent mean ± SD from at least six individual rats *, <i>P</i><0.05; **, <i>P</i><0.01; ***, <i>P</i><0.001 for comparison with INTACT group (panel A) and for comparison with CH group (panel B); +, <i>P</i><0.05; ++, <i>P</i><0.01; +++, <i>P</i><0.001 for comparison with vehicle-treated TX group. <b>̂̂̂</b>, <i>P</i><0.001 for comparison with WP group.</p

Effects of neonatal hypothyroidism on mRNA expression levels of genes related with lipid metabolism in adult rat liver.

<p>On PND80, the hepatic mRNA levels of PPARα (A), CPT1 (B), ME (C), SREBP1c (D), ACC1 (E), FAS (F), CYP4FI (G), AOX (H), and L-FABP (I) were measured by qPCR in CH, age-matched INTACT, or weight-paired (WP) control groups. The mean mRNA expression level of each gene in the INTACT group is defined as 1, with all other expression values reported relative to this level. Bars represent mean ± SD from at least five individual animals. *, <i>P</i><0.05; ***, <i>P</i><0.001 for comparison with INTACT group. <b>++</b>, <i>P</i><0.01; <b>+++</b>, <i>P</i><0.001 for comparison with WP group.</p

Effects of congenital hypothyroidism on mRNA expression levels of genes involved in bile acid synthesis in adult rat liver.

<p>On PND80, the hepatic mRNA levels of CYP7A1 (A), CYP27A1 (B), CYP8B1 (C), FXR (D), and SHP (E) were measured by qPCR in CH, age-matched INTACT or weight-paired (WP) control groups. The mean mRNA expression level of each gene in the INTACT group is defined as 1, with all other expression values reported relative to this level. Bars represent mean ± SD from at least five individual animals. **, <i>P</i><0.01; ***, <i>P</i><0.001 for comparison with INTACT group. <b>+++</b>, <i>P</i><0.001 for comparison with WP group.</p