PITUITARY GONADOTROPHINS 



WITHIN THE past decade various gonadotrophic hormones have been puri- 

 fied considerably. E\idence for purity of the active principles from 

 human pregnancy urine and serum of pregnant mares has been reported.'"* 

 Purification of a complete gonadotrophin from pituitary extracts has not been 

 reported, while in several laboratories fractionation of such extracts has 

 yielded two separate gonadotrophic principles of a high degree of activity.""'" 

 The biological effects of these two principles are similar though not identical 

 in character with those ascribed ten years ago by Fevold and his co-workers" to 

 their follicle-stimulating (FSH) and luteinizing (LH) hormone respectively. 

 The close resemblance in the activity of the purified preparations obtained 

 by different methods in a number of laboratories does not lend support to the 

 assumption that these two active principles may represent artifacts or split 

 products of a macromolecule. It is recognized, however, that the isolation of 

 these proteins from the pituitary does not prove that they actually are secreted 

 in this form. Evidence has been presented that the hormones liberated by 

 intact glandular tissue are quantitatively and qualitatively superior to those 

 extracted from stich tissue.^* However, the concentration of pituitary gonado- 

 trophins in the blood stream is so low that no atcempts to purify and, possibly, 

 fractionate these hormones, have as yet been reported. The fact that the type 

 of gonadotrophic activity in the body fluids of normal (nonpregnant) animals 

 may show great variations within the life cycle of the animal, primarily con- 

 trolled by its gonads, tends to favor the assumption of two hormones actually 

 being secreted in varying relative amounts by the pituitary. With the study 

 of these circulating hormones being delegated to the future, a review of the 

 properties of the gonadotrophins isolated from pituitary extracts will be 

 attempted here. 



Physicochemical Properties of FSH and ICSH (LH) 



(Foil iciest i mulatitig hormone mid interstitial-cell-stiinidaliug honnone) 



All gonadotrophins are glycoproteins; they can be effectively separated from 

 inert protein and most other hormones by their stability and solubility in 

 alcohol-water or acetone-water mixtures. Extraction of acetone-dried sheep 

 glands with 40 per cent alcohol has proven most successful.''" Methods of 

 fractionation of the gonadotrophic complex are based on the fact that the 

 FSH is more soluble in salt solutions than the ICSH. Thus, repeated precipita- 

 tion of the proteins with ammonium sulfate at half and two-thirds saturation, 

 as well as fractionation with sodium sulfate at pH 4.4, achieves separation of 

 the two principles. From the lower salt fractions a pure protein was isolated 

 which contained the ICSH activity.'""'-""''' Comparison of the final products 

 obtained from sheep'""" and pig piiuitaries"" has shown these to be quanti- 



