Which hormone interact with membrane bound receptors exhibit the following properties except?

1 Types of Hormone Molecules

Hormones are heterogeneous in their molecular size, chemical properties, and pathways of synthesis. Nitric oxide (NO; see Chapter 15) is at one extreme of the size range; the pituitary gonadotropins (Chapter 3) consisting of two subunits are among the largest of the protein hormones with molecular weights ranging between 25 and 36 kDa, depending on the extent of added carbohydrates (glycosylation). Peptide or protein hormones range from three amino acids (TRH, Chapter 3) to over 100 per subunit. Thyroid hormone (Chapter 5) and epinephrine (Chapter 11) are derived from the amino acid tyrosine. Steroid hormones and vitamin D and its metabolites are derived from cholesterol or 7-dehydrocholesterol, respectively (Chapter 2). Arachidonic acid, cleaved from membrane phospholipids, is the main precursor of the prostaglandins and other eicosanoids (Chapter 8).

The initial step in the action of a hormone, the interaction with its receptor, depends to some extent on its chemical nature. Peptide and protein hormones have receptors that are membrane-spanning proteins so that the molecule does not have to enter the cell, but can deliver its message on the outside where it will be conveyed to the interior of the cell by structural changes in the receptor protein. Steroid hormones, considered to be soluble in the phospholipid bilayer, can enter the cell so that the receptors for these hormones are located either in the cytoplasm or the nucleus of the cell. The actions of these hormones are propagated by interaction of the receptor with nuclear proteins and DNA. The amino acid-derived hormones differ from one another: thyroid hormone has an intracellular receptor similar to those for the steroid hormones and epinephrine interacts with its membrane receptor.

Thus, the hormonal messaging systems have evolved using a variety of types of molecules and mechanisms of actions. Understanding these in settings of particular systems is a major focus of this book.

Pharmacology and toxicology

The hormones of the anterior lobe of the pituitary gland regulate hormone released by the peripheral hormone glands. The release of anterior pituitary hormones is controlled by the hypothalamic releasing hormones. Because of their high molecular weight, pituitary hormones do not cross the placenta. Therefore, a direct effect on the fetus is not to be expected. The following hormones are released from the anterior pituitary gland.

Growth hormone (GH, somatropin, STH)

This has effects on somatic growth and on metabolism. A hormone similar structurally and functionally to GH is produced in increasing quantities by the placenta in advanced pregnancy. It is referred to as human placental lactogen (HPL) or, less often, as human chorionic somatomammotropin (HCS). Functionally, this hormone is similar to prolactin.

Prolactin is a polypeptidic hormone whose main role consists of the stimulation of lactation in the postpartum period. A physiological increase in prolactin secretion occurs during pregnancy and lactation, but also in hypothalamic and pituitary diseases. Prolactin has no therapeutic use.

Follicle stimulating hormone (FSH, urofollitrophin, follitrophin-α, follitrophin-β)

This stimulates growth and maturation of the ovarian follicle, and granulosa cell release of estrogen. Luteinizing hormone (LH) stimulates ovulation. During pregnancy, human chorionic gonadotrophin (hCG), which is analogous to LH, is synthesized in the placenta, and is responsible for maintaining the corpus luteum of pregnancy. FSH and a mixture of FSH and LH have been used therapeutically. Human menopause gonadotrophins (hMG) and hCG are two of these mixtures (analogs are menotropin and urogonadotropin). These hormones are used for ovulation induction and for additional support of the corpus luteum. Inducing ovulation with gonadotrophins can lead to multiple pregnancies; of these, 5–6% involve triplets (Scialli 1986). Two publications report on a rare complex of multiple malformations and four cases of neuroblastoma in infants below 1 year, born of pregnancies involving exposure to gonadotrophins (Mandel 1994, Litwin 1991). These findings were not confirmed in other studies, nor were other pregnancy risks or abnormalities in early childhood and pubertal development associated with use of these agents for ovulation induction.

Thyroid stimulating hormone (thyrotropin, TSH)

This stimulates the synthesis and release of thyroxine.

Adrenocorticotropic hormone (ACTH, tetracosactid)

This stimulates the synthesis and release of the glucocorticoids and mineralocorticoids in the adrenal cortex.

Melatonin is secreted by the pineal gland. Melatonin secretion is regulated on the basis of photic stimuli; in the absence of photic stimuli (at night), melatonin secretion increases. Melatonin coordinates biological rhythms. It also stimulates progesterone secretion, inhibits prostaglandin synthesis, and has (experimentally) a tocolytic effect (Ayar 2001). The human fetal suprachiasmatic nucleus expresses melatonin-binding sites, and is therefore likely to be affected by both endogenous and exogenous melatonin, with consequences for the prenatal and postnatal expression and entrainment of circadian rhythms. The relevance of melatonin to the maintenance of pregnancy at the feto-maternal interface has been investigated, and results suggest that melatonin seems to regulate the human placental function in a paracrine/autocrine manner (Iwasaki 2005). There is insufficient experience with the therapeutic use of melatonin (for instance, for prevention of jetlag after intercontinental flights) in pregnancy.

Recommendation.

There are no indications for using anterior pituitary hormones during an already existing pregnancy. Inadvertent use is not grounds for pregnancy termination or for invasive diagnostic procedures.

Hormones and the Immune Response

While hormones, especially estrogens, are considered to be important contributors in the aberrations of the immune response and expression of disease, their exact molecular role and mechanisms of action are still poorly understood. Studies have shown the effect of hormones on cytokine production by various immune cells, gene regulation in T cells, immunoglobulin production by B lymphocytes and function of granulocytes and NK cells.5,6 Some of the first direct molecular evidence into the role of estrogen in autoimmunity came from studies performed in non-autoimmune mice transgenic for the heavy chain of a pathogenic anti-dsDNA antibody. Estrogen upregulates expression of the antiapoptotic molecule Bcl-2 and promotes survival of autoreactive B cells, allowing their escape from tolerance induction.7 An important aspect of B-cell activation is the antibody affinity maturation, which involves somatic hypermutation and class-switch recombination, both of which require the activation-induced deaminase (AID) enzyme.8 Estrogen was shown to directly activate transcription of AID through binding elements within the AID promoter.9 Furthermore, estrogen enables the survival and persistence of autoreactive T cells by downregulating FasL and suppressing activation-induced cell death of human SLE T cells.10

Studies performed in human peripheral blood T cells have shown that estrogen increases the expression of calcineurin mRNA and the encoded protein phosphatase (PP) 2B activity in an ER-dependent manner. PP2B induces dephosphorylation of the nuclear factor of activated T cells transcription factor and subsequent nuclear translocation and binding to target genes such as CD40L. Estrogen may contribute to the increased T cell cognate help to autoreactive B cells, as estradiol administration was shown to upregulate the expression of CD40L in T cells from lupus patients but not healthy individuals.11 Exposure of normal human peripheral blood T cells to estradiol led to increased expression of the transcriptional repressor cyclic AMP response element modulator (CREM) alpha and suppression of interleukin (IL-2) cytokine production.12,13

Cytokine abnormalities are an important component of the aberrant immune response in patients with SLE. The immune response in SLE is characterized by a Th2 type of cytokine environment, such that cytokines IL-4, IL-6, and IL-10 are increased in serum from patients. In addition, increased serum levels of the proinflammatory cytokine IL-17 and increased proportion of Th17 differentiated cells are observed in SLE patients and thought to contribute to autoimmune disease pathogenesis.14 Estrogen is known to regulate the immune system by modulating cytokine production. High doses of estrogen are known to promote Th2 cytokine (IL-4, IL-10, TGFβ) production. High serum estrogen levels correlated with low IL-2 levels in the lupus-prone NZB/NZW mice. Furthermore, estrogen treatment increased tumor necrosis factor (TNF) and IL-6 levels after challenge with lipopolysaccharide (LPS) in both normal and lupus-prone MRL/lpr mice; these effects were reversed by the selective ER modulator tamoxifen. Animal studies have shown that mice treated with synthetic estrogen were susceptible to Listeria monocytogenes bacterial infection and their splenocytes produced less IL-2, while increased IL-17 production was seen in splenocytes from estrogen-treated mice.15,16 Estrogen is also known to regulate the proinflammatory cytokine IFNγ and was shown to enhance CD4 responses and IFNγ producing cells from lymph nodes,17 and the Th1 differentiation transcription factor T-bet was upregulated by estrogen in murine splenocytes.18

Dendritic cells (DCs) are initiators of the innate as well as adaptive immune responses and abundantly express the pattern recognition Toll-like receptors (TLRs). TLR7- and TLR9-deficient lupus-prone mice exhibit reduced disease, indicating that TLRs are important in lupus pathogenesis. DCs are defective in SLE in both humans and mice exhibiting an overstimulated phenotype and function, with increased expression of major histocompatibility complexes (MHCs) as well as costimulatory molecules CD80/86.19 Estrogen can modulate DC differentiation and function in several ways: alter the expression of MHC proteins, costimulatory molecules, or TLR; regulate cytokine production by DCs directly or indirectly via other cell types; and modulate migratory function through changes in cytokine or chemokine production. Furthermore, estrogen is required for the activation and differentiation of DCs, specifically those bearing features of a Langerhan cell like DC.20

Besides the direct role of estrogen on the immune system, another notion is that the regulatory mechanisms that normally control the estrogen-induced excitation of the immune response may be abnormal in SLE patients. To this end, DNA microarray analysis of genes expressed in the peripheral blood mononuclear cells during the menstrual cycle of healthy women were compared to those from women with SLE and showed interesting differences. Specifically, tumor necrosis factor receptor superfamily member 14 (TNFRSF14; synonym: herpes virus entry mediator, HVEM) was increased in correlation with increasing serum estrogen levels in healthy women but not in SLE patients. TNFRSF14 is a ligand for B and T lymphocyte attenuator, an inhibitory receptor which dampens lymphocyte activation and is important in maintaining immune homeostasis. These results suggest that the mechanisms that regulate the immune activating effects of estrogen may be defective in SLE patients.21

5.7 Embryonic Vs. Maternal Hormones

Hormones of maternal and offspring origin are structurally identical, so that receptors cannot distinguish their origin and will respond equally to both. Before the onset of endogenous steroid hormone production, only maternal hormones can act on the receptors that are present already at this stage. Therefore, this may be a special sensitive period for the effects of maternal hormones on offspring. Once embryos begin producing the same hormones, maternal hormones act with the endogenous hormones. Maternal hormones may have specific effects if the embryo does not yet produce a given hormone or if the maternal hormone is metabolized to a different form before, during, or after uptake by the embryo. Maternal hormones also may affect endogenous production of hormones through effects on synthesizing or metabolizing enzymes or alter the responsiveness to hormones due to effects on hormone receptors.

30.6.4.2 Growth hormone–releasing hormone

GHRH or somatoliberin is a peptide with 47 amino acid residues. It is synthesized as prepro-GHRH and is cleaved to pro-GHRH and then to GHRH (see Figure 30.10). The structure of GHRH is similar across avian species (see Figure 30.10).

GHRH is expressed in the avian hypothalamus and also in the small intestine, kidneys, lung, ovary, anterior pituitary gland, spleen, and testes (chicken: Wang et al., 2007). There is high expression of GHRH in the embryo day eight, but, subsequently, this declines to a low plateau level on days 12–20 (Wang et al., 2006). GHRH increases GH release in vivo and in vitro (chicken: Scanes et al., 1984). Avian somatotropes respond to GHRH with increased intracellular calcium (chicken: Scanes et al., 2007) (Table 30.7).

Table 30.7. Effect of chicken growth hormone on the oviduct in young female chickens.

ControlChicken growth hormoneaBody weight kg1.50 ± 0.021.52 ± 0.02Oviductal characteristicsRelative oviduct weight%0.43 ± 0.111.22 ± 0.27bProliferating cells as % of control100 ± 3.2102 ± 3.0Apoptotic cells as % of control100 ± 2.863 ± 2.3cExpression of ovalbumin in magnum as % of control100 ± 18309 ± 68bExpression of ovocalyxin-32 in shell gland as % of control100 ± 16703 ± 234b

Calculated from Hrabia, A., Leśniak-Walentyn, A., Sechman, A., Gertler, A., 2014b. Chicken oviduct-the target tissue for growth hormone action: effect on cell proliferation and apoptosis and on the gene expression of some oviduct-specific proteins. Cell Tissue Res. 357, 363–372.

8. REGULATION OF HORMONE LEVELS (HORMONAL HOMEOSTASIS)

Hormones are required for specific actions at specific times in growth and development, and it is important for the plant, not only to be able to synthesize the hormone, but also to inactivate it when not needed. Furthermore, hormones are required in small amounts, picomolar to micromolar quantities, and plants often produce far more bioactive hormone than is actually required. Evidence comes from synthesis mutants that are leaky, i.e., the mutated allele is not a null allele, but is still able to produce a partly functional enzyme. Such leaky mutants often produce enough hormone to carry out many responses, although perhaps not all. Thus, the regulation of endogenous levels of bioactive hormones, or hormone homeostasis, is of prime importance to normal growth and development of plants.

Plants use three mechanisms to regulate endogenous levels of hormone: (i) regulation of the rate of hormone synthesis, (ii) inactivation of the hormone by conjugation with carbohydrates, amino acids, or peptides, and (iii) an irreversible breakdown of the hormone. Other means of regulating the levels of free hormone include transport to other parts of the plant and/or inactivation and storage in some compartment (Fig. 5-7).

Inactivation or breakdown of hormones and compartmentation in an inactive form are strategies that are regularly utilized. Similar inactivation or breakdown is also seen if plant tissues are presented with exogenous hormone in unnaturally large quantities or if the plant produces an excessive amount of the hormone as a result of a mutation or genetic transformation.

Before leaving this section, it is important to emphasize that mutants deficient in a particular hormone, or mutants or plants that have been transformed to overproduce a hormone, are invaluable tools in deciphering the physiological and/or biochemical roles of that hormone in plant growth and development. They point out with great specificity the particular roles a hormone plays and far surpass in accuracy the conclusions drawn from supplying the hormone to a whole plant or plant tissues and noting the effect(s).

Abstract

CHH, MIH, VIH, and MOIH are produced by the X-organ sinus gland complex and are members of the CHH family peptides. These peptides are mostly 72–78 aa residues long, having six conserved cysteine residues that form three intramolecular disulfide bonds. Most of the CHH family is type I and consists of 72 aa residues with a C-terminal amide. CHH controls hemolymph glucose levels as a hyperglycemic factor. Hyperglycemia is a result of mobilization of glycogen in the hepatopancreas and muscle. Recent studies have revealed that CHH has pleiotropic functions such as MIH, MOIH, and VIH activities. MIH, VIH, and MOIH are grouped as type II, because they have a characteristic glycine residue at position 12. MIH, VIH, and MOIH are longer in length than CHH. MIH inhibits molting by suppressing synthesis and/or secretion of ecdysteroids by the Y-organ. VIH inhibits vitellogenin synthesis by the ovary and/or hepatopancreas. MOIH inhibits methyl farnesoate synthesis and/or secretion by the mandibular organ.

Which hormones interact with membrane bound receptors?

Which of the following hormone does not interact with membrane bound receptor?

Which group of hormones interact with membrane bound receptors and use second messengers?

Which of the following has membrane bound receptors?