Thyroid hormone receptors and ligand, tissue distribution and sexual behavior

The thyroid hormones (THs) triiodothyronine (T3) and tetraiodothyronine, or thyroxine (T4), not only dramatically impact on development and differentiation, but also on the sexual and reproductive function. There is large body of literature, in fact, on the effects of THs on the reproductive function in both humans (Poppe and Velkeniers, 2004; Wajner et al., 2009) and animals (Hapon et al., 2010; Nelson et al., 2011). For a long time the gonads were thought to be unresponsive to THs, but TH receptors (TR) were discovered in rat (Jannini et al., 1990; Palmero et al., 1988) and then in human testis (Jannini et al., 2000). In women, the association of menstrual disturbance with thyroid disease was described as early as 1840 by von Basedow, but the discovery of TRs in the ovary was carried out at the end of last century (Wakim et al., 1994b). Therefore, the link between thyroid and reproductive function was well established. Since then, research has shown that thyroid dysfunction is associated with an adverse effect on fertility, both in men (Wagner et al., 2009) and women (Dittrich et al., 2011). There is also evidence that THs can affect the sex steroid hormone axis (Bagamasbad and Denver, 2011), consequently sexual hormones and the pituitary gland can mediate the action of THs on the reproductive physiology. While the effects of THs on fertility have been widely studied, little is known about their influence on sexual function. In the last few years, an increasing number of evidences have shown the influence of THs on male sexual function, particularly on ejaculation control as well on desire and erectile function (Carani et al., 2005; Corona et al., 2012b; Di Sante et al., 2016). The female sexual function and the relationship with thyroid function is still less studied. Furthermore, studies conducted on animals have shown the presence of TRs in the male (Carosa et al., 2010) and female genitalia (Rodriguez-Castelan et al., 2017). Moreover, knockout mice for TRs showed alterations in sexual behavior (Dellovade et al., 2000). The purpose of this review is to summarize and discuss the available data on the influence of THs on male and female sexual function to understand the molecular mechanisms of the influence of the thyroid gland on sexual behavior and function

Regulation of the juvenile hormone titre in the Colorado potato beetle

Three main topics were investigated in regulation of the titre of juvenile hormone in haemolymph of the Colorado potato beetle ( Leptinotarsa decemlineata Say): enzymic breakdown of the hormone; binding and protection of the hormone by carrier proteins; the synthetic capacity of the corpora allata.Juvenile hormone was broken down by two major pathways: ester hydrolysis by esterases and hydration of the epoxide group by epoxide hydratases in tissue. In haemolymph of the beetle, juvenile hormone is solely broken down by juvenile hormone esterases. An in vitro method was developed to measure the catalytic activity of juvenile hormone esterase from haemolymph. High activities were observed in fourth-instar larvae and in beetles just before diapause. Lower activities were found in third- instar larvae and in beetles reared with long days, at diapause and after diapause. The juvenile hormone esterase was insensitive to diisopropylfluorophosphate (DFP), an inhibitor used to distinguish between carboxylesterases and esterases specific to juvenile hormone. Electrophoresis of the esterase from haemolymph showed one or more esterases specific to juvenile hormone.The short half-life of juvenile hormone measured in vivo and in vitro in the haemolymph and inhibition studies with Triton X-100 suggests that juvenile hormone esterases in haemolymph govern breakdown. Activities of juvenile hormone esterase correlate well with the juvenile hormone titre.The sharp changes in juvenile hormone esterase suggest that esterase activity is regulated. The mechanism was studied by supplying juvenile hormone and by microsurgery. Treatment of diapausing beetles with juvenile hormone itself or analogues caused an increase in activity of juvenile hormone esterase within 24 h. Ligation or removal of corpora allata suggested that this induction was an indirect effect of juvenile hormone. Transfer from short day to long day and treatment with hormone of beetles reared with short days prevented high activity of juvenile hormone esterase. Removal of corpora allata at emergence from beetles reared with short days resulted in the same. In beetles reared with short days the titre of hormone during the first days after adult emergence probably induces the rise in esterase. Esterase activity is thus most likely controlled indirectly by the hormone, via a centre in the brains (hormostate). The level of esterase activity is probably dependent on the sensitivity of this hormostate and on the titre of the juvenile hormone.In several insects juvenile hormone is transported bound to carrier proteins. In haemolymph of larval and adult Colorado potato beetles lipoproteins of high molecular weight (>100,00 daltons) were found, capable of binding juvenile hormone, its analogues, and palmitic acid. The lipoproteins were partially separated by gel permeation chromatography and electrophoresis on polyacrylamide gel. The binding characteristics of the lipoproteins indicate low affinity (K d ≈10 -5 M), low specificity and high binding capacity. The juvenile hormone complexed to lipoproteins was protected against esterases from haemolymph to some extent. Thus these carrier lipoproteins probably play little role in the regulation of the titre of juvenile hormone.In the last part of our investigations the activity of the corpora allata was measured in vitro. High activities were observed in beetles reared with long days and in beetles after emergence. In beetles reared with short days, amounts of hormone produced were intermediate until Day 6 after emergence, thereafter declining to a low value. During diapause, production remained low. The production by corpus allatum and the activity of juvenile hormone esterase were in good agreement with the titre of juvenile hormone. The corpora allata are probably the primary regulator of the hormone titre in the Colorado potato beetle.<p/

Development of eye colors in Drosophila: some properties of the hormones concerned

The substance inducing the production of pigment in the eyes of vermilion brown mutants of Drosophila melanogaster has been shown to be a relatively stable chemical entity possessing true hormone-like activity. A simple method for obtaining hormone solutions has been developed involving extraction of dried wild type Drosophila pupae with ethyl alcohol and water. A logarithmic proportionality has been found to exist between the amount of hormone and the induced eye color. This relationship provides a simple method for the quantitative determination of hormone concentration in given extracts. Larvae and pupae of D. melanogaster contain an intracellular enzyme which inactivates the hormone in the presence of molecular oxygen. The hormone is not oxidized under ordinary conditions with either molecular oxygen or hydrogen peroxide. The hormone has been found to be an amphoteric compound with both acidic and basic groups and with a molecular weight between 400 and 600. The solubility and precipitation reactions of the hormone suggest its amino acid-like nature. However, the instability to heat, acid, and alkali, and its rather restricted occurrence indicate a rather complex specific structure

The effects of environmental stress on the physiology of growth in rainbow trout, Salmo gairderi Richardson

There is little doubt that both mammalian and teleost growth hormones can accelerate growth and increase food conversion efficiency in all commonly-reared species of salmonid fish. In those vertebrates that have been closely studied (predominantly mammals), the pituitary hormone somatotropin (GH or growth hormone) is a prime determinant of somatic growth. The hormone stimulates protein biosynthesis and tissue growth, enhances lipid utilization and lipid release from the adipose tissues (a protein-sparing effect) and suppresses the peripheral utilization of glucose. The present study is a prerequisite for future work on growth hormone physiology in salmonids and should contribute to our understanding of the mechanisms of growth suppression in stressed fish. Plasma growth hormone (GH) levels were measured in rainbow trout using a radioimmunoassay developed against chinook salmon growth hormone

An increase in N-Ras expression is associated with development of hormone refractory prostate cancer in a subset of patients

Protein expression of H, K and N-Ras was assessed in hormone sensitive and hormone refractory prostate tumour pairs from 61 patients by immunohistochemistry. Expression of H-Ras and K- Ras was not associated with any known clinical parameters. In contrast an increase in N-Ras membrane expression in the transition from hormone sensitive to hormone refractory prostate cancer was associated with shorter time to relapse (p=0.01) and shorter disease specific survival (p=0.008). In addition, patients with an increase in N-Ras membrane expression had lower levels of PSA at relapse (p=0.02) and expression correlated with phosphorylated MAP kinase (p=0.010) and proliferation index (Ki67, p=0.02). These results suggest that in a subgroup patients N-Ras expression is associated with development of hormone refractory prostate cancer via activation of the MAP kinase cascade

Gene amplifications associated with the development of hormone- resistant prostate cancer

Purpose: Hormone resistance remains a significant clinical problem in prostate cancer with few therapeutic options. Research into mechanisms of hormone resistance is essential. Experimental Design: We analyzed 38 paired (prehormone/posthormone resistance) prostate cancer samples using the Vysis GenoSensor. Archival microdissected tumor DNA was extracted, amplified, labeled, and hybridized to Amplione I DNA microarrays containing 57 oncogenes. Results: Genetic instability increased during progression from hormone-sensitive to hormone-resistant cancer (P = 0.008). Amplification frequencies of 15 genes (TERC, MYBL3, HRAS, PI3KCA, JUNB, LAMC2, RAF1, MYC, GARP, SAS, FGFR1, PGY1, MYCL1, MYB, FGR) increased by greater than 10% during hormone escape. Receptor tyrosine kinases were amplified in 73% of cases; this was unrelated to development of hormone resistance. However, downstream receptor tyrosine kinase signaling pathways showed increased amplification rates in resistant tumors for the mitogen-activated protein kinase (FGR/Src-2, HRAS, and RAF1; P = 0.005) and phosphatidylinositol 3'-kinase pathways (FGR/ Src-2, PI3K, and Akt; P = 0.046). Transcription factors regulated by these pathways were also more frequently amplified after escape (MYC family: 21% before versus 63% after, P = 0.027; MYB family: 26 % before versus 53 % after, P = 0.18). Conclusions: Development of clinical hormone escape is linked to phosphatidylinositol 3'-kinase and mitogen-activated protein kinase pathways. These pathways may function independently of the androgen receptor or via androgen receptor activation by phosphorylation, providing novel therapeutic targets

Changes in epithelial proportions and transcriptional state underlie major premenopausal breast cancer risks

The human breast undergoes lifelong remodeling in response to estrogen and progesterone, but hormone exposure also increases breast cancer risk. Here, we use single-cell analysis to identify distinct mechanisms through which breast composition and cell state affect hormone signaling. We show that prior pregnancy reduces the transcriptional response of hormone-responsive (HR+) epithelial cells, whereas high body mass index (BMI) reduces overall HR+ cell proportions. These distinct changes both impact neighboring cells by effectively reducing the magnitude of paracrine signals originating from HR+ cells. Because pregnancy and high BMI are known to protect against hormone-dependent breast cancer in premenopausal women, our findings directly link breast cancer risk with person-to-person heterogeneity in hormone responsiveness. More broadly, our findings illustrate how cell proportions and cell state can collectively impact cell communities through the action of cell-to-cell signaling networks

Estradiol and testosterone levels in patients undergoing partial hepatectomy - A possible signal for hepatic regeneration?

In five adult male patients undergoing a 40-60% partial hepatectomy, serum sex hormone levels before and after hepatic resection were determined. Blood was drawn immediately prior to each surgical procedure and at specified time points postoperatively. Compared to hormone levels found prior to surgery, following major hepatic resection, estradiol levels increase at 24 and 48 hr, while testosterone levels decline, being significantly reduced at 96 and 144 hr. These data demonstrate that adult males who undergo a 40-60% partial hepatectomy experience alterations in their sex hormone levels similar to those observed in male rats following a 70% hepatectomy. These changes in sex hormone levels have been associated in animals with an alteration of the sex hormone receptor status of the liver that is thought to participate in the initiation of the regenerative response. These studies suggest, but do not prove, that in man, as in the case of the rat, sex hormones may participate in the initiation of or at least modulate in part the regenerative response that occurs following a major hepatic resection. © 1989 Plenum Publishing Corporation