Hormones species specificity

This approach appears somewhat irrational and without much scientific merit, since many of these new molecules are minimally toxic or nontoxic by this sort of acute evaluation. As in the case of interferons or monoclonal antibodies, the toxic effects observed in humans might not be predicted from safety assessments in rodents. An appropriate test species should be selected. Is the rat or mouse the appropriate species to evaluate a species-specific rDNA protein such as human growth hormone or interferons, or would nonhuman primates be more suitable Does the nonhuman primate really offer any advantages There is some consensus that the nonhuman primate may be a more appropriate species for testing some rDNA human proteins. 

Now we can ask what is likely to happen to the three-dimensional structure of a protein if we make a conservative replacement of one amino acid for another in the primary structnre. A conservative replacement involves, for example, substitution of one nonpolar amino acid for another, or replacement of one charged amino acid for another. Intnitively, one would expect that conservative replacements would have rather little effect on three-dimensional protein structure. If an isoleucine is replaced by a valine or leucine, the structnral modification is modest. The side chains of all of these amino acids are hydrophobic and will be content to sit in the molecnlar interior. This expectation is borne out in practice. We have noted earlier that there are many different molecnles of cytochrome c in nature, all of which serve the same basic function and all of which have similar three-dimensional structnres. We have also noted the species specificity of insulins among mammalian species. Here too we find a number of conservative changes in the primary structure of the hormone. Although there are exceptions, as a general rule conservative changes in the primary structnre of proteins are consistent with maintenance of the three-dimensional structures of proteins and the associated biological functions. 

Estradiol subsequently builds up in the blood and first (within 2 to 12 hours) reduces the levels of follicle-stimulating hormone (FSH) and the amplitude of LH pulses, then (within 12 to 48 hours) causes preovulatory surges of LH and FSH. The former promotes ovulation and development of a corpus luteum (reviewed in Martin et ah, 1986). Two compounds have been indicated in the effect of the odor of ram s fleece on LH secretion in anestrous ewes. These are 1,2-hexadecanediol and 1,2-octadecanediol. In Merino sheep at least, maximum stimulation of ovulation requires full exposure to a ram, such as fenceline contact in pastures. Olfactory cues from the ram s wool, presented in a facemask for the ewe, are ineffective by themselves visual and tactile stimuli are also important. The Merino breed does not rely as much on olfactory cues as other breeds of sheep (Pearce and Oldham, 1988). The effect is not necessarily species specific hair extract from male goats stimulates LH release in ewes. For this effect, the accessory olfactory system is not necessary (Signoret etah, 1989). 

Sorensen, P. W., Irvine, I. A. S., Scott, A. P., and Stacey, N. E. (1992). Electrophysiologi-cal measures of olfactory sensitivity suggest that goldfish and other fish use species-specific mixtures of hormones and their metabolites as pheromones. In Chemical Signals in Vertebrates, vol. 6, ed. R. L. Doty and D. Miiller-Schwarze, pp. 357-354. New York Plenum. 

Insulin therefore consists of two peptide chains that are connected by two disulfide bonds, since the C-peptide is cleaved off. There are some species-specific differences in the amino acid sequence of the hormone. X-ray diffraction studies have shown that insulin occurs as a hexameric protein containing two Zn atoms. The dimers are first held by four hydrogen bonds and a hydrophobic bond along the sequence in the form of an antiparallel P sheet. The dimers then bind by interaction of the B -Ala, B -Leu, and B -Val residues. The core of the hexamer contains water. 

Hormones produced hy one species usually show similar activity in other species. The hormones showing greatest species specificity are proteins or conjugated proteins. 

Human ACTH is a single peptide chain of 39 amino acids. The amino terminal portion containing amino acids 1-24 is necessary for full biologic activity. The remaining amino acids (25-39) confer species specificity. Synthetic human ACTHi 24 is known as cosyntropin. The amino terminal amino acids 1-13 are identical to melanocyte-stimulating hormone (cr-MSH), which has been found in animals but not in humans. In states of excessive pituitary ACTH secretion (Addison s disease or an ACTH-secreting pituitary tumor), hyperpigmentation—caused by the -MSH activity intrinsic to ACTH—may be noted. 

The ACTH sequence can be formally subdivided into various sections of differing biological significance. The N-terminal section 1-10 represents the active center, while sequence 11-18 is responsible for receptor binding. The C-terminal section 25-39 contains the hormonal information for species specificity and for antigenicity. 

For the pituitary hormones, and pancreatic hormones, analytical methods are in general available with species specific reagents for the mouse, rat, dog, pig and to a limited extent for rabbit. Steroid hormones can be measured readily by an array of analytical methods. Application of gene arrays and studies on gene expression are not recommended for single-dose experiments, repeated dose exposure is required (3-7 days). 

This section describes the measurement of pituitary hormones in the context of repeated dose studies of 1-4 weeks duration. When performing an endocrine safety pharmacology study in rats it is advisable to determine pituitary hormone concentrations at autopsy, because in this species specific pituitary hormone assays are readily available. The time point two hours after last dosing is in general suitable, when changes in pituitary hormone contents need to be assessed. 

Mating in most species of moths is mediated through the production and release of species-specific sex pheromones by the females and, in a majority of the moths, reproductive activity is limited to the hours of darkness. To achieve this diurnal periodicity of mating, production of sex pheromone must also be synchronized (JL). In the corn earworm, Helicoverpa Heliothls) zea, and in many other species of moths, this synchronization is affected by a factor produced in the head of the female (2.). The factor was identified as a peptide hormone, produced in the suboesophageal ganglion (SOG) and most likely... 

R = Et) by a sequence of standard reactions. Using precisely the same methodology, Corey and Yamamoto have accomplished short and stereospecific syntheses of farnesol (25) and a positional isomer of Cecropia juvenile hormone (26) as outlined in Scheme 1. A preliminary examination of the biological activity of (26) indicates that it is very active and species specific. 

The hypotlialamic peptides, in contrast to some pituitary tropic hormones such as the gonadotropins, are not entirely species specific. Porcine Gn-RH and TRH have been shown to have an effect in humans. The availability of highly purified and synthetic releasing hormones has important diagnostic and therapeutic implications. CRH, GH-RH, Gn-RH, and TRH have all been used to test for pituitary hormone... 

---