PHYSIOLOGY OF ANTERIOR HYPOPHYSIS 



243 



trophic hormone (STH) were negative at 

 the dosage level of 0.5 mg. of the FSH prep- 

 aration. Latest among studies of purifica- 

 tion of FSH is that of Ellis (1958). Using 

 metaphosphoric acid and ethanol precipita- 

 tion, he obtained a satisfactory concentrate 

 of FSH which he was able to purify further 

 by chromatography on diethylaminoethyl 

 cellulose and starch electrophoresis at pH 

 4. This FSH preparation was electrophoreti- 

 cally monodisperse, free of LH and TSH, 

 and had 30 to 40 times the potency of Ar- 

 mour Standard. 



The development of satisfactory proce- 

 dures for the isolation of FSH has been an 

 exceedingly difficult in-ol)lcm and most 

 workers are agreed that the methods are 

 not finalized and that no product thus far 

 obtained has satisfied all the modern cri- 

 teria of purity. Certainly, also, there are too 

 few studies with the highly imrified prepara- 

 tions to establish the biologic characteristics 

 of this hormone. The difficulty in ascribing 

 to FSH the status of a homogeneous chemi- 

 cal compound is emphasized l)y the work of 

 Steelman, Lamont and Baltcs (1955, 1956) 

 and by Steelman (1958). Using jiancreatin 

 digestion followed by chromatography on 

 hydroxyl apatite, they obtained 3 FSH frac- 

 tions, all with considerable relative activity, 

 and are in doubt as to whether the ])re- 

 chromatographed material can be regarded 

 as homogeneous. 



There is no doubt, as we survey the verte- 

 brates as a whole, that there is a pituitary 

 factor immediately concerned in follicular 

 maturatibiTancl to this extent follicle-stim- 

 ulating hormone is a proper term. Caution 

 should be exercised lest terminologic con- 

 venience be confused with the fact. Never- 

 theless, with modern methods of protein 

 research it is very probable that a follicle- 

 stimulating hormone will be isolated soon, 

 and perhaps characterized as a polypei^tide 

 with known amino acid composition and 

 sequence. 



Whatever the precise nature of FSH, it is 

 carried to its target organs by the blood. A 

 preliminary study (Mc Arthur, Pennell, An- 

 toniades, Ingersoll, Oncley and Ulfelder, 

 1956) of postmenopausal plasma fraction- 

 ated by the cold ethanol method of Cohn 

 has revealed that the gonadotrophic ac- 

 tivity, pituitary in origin and presumed to 



comprise mainly FSH, is contained in Frac- 

 tions II and III. This means that FSH as 

 such may well be in combination with pro- 

 teins not only in the pituitary but also in 

 the blood stream. 



2. Physiologic Effects in Females 



One activity of the anterior lobe of the 

 pituitary brings about the maturation of 

 egg-bearing ovarian follicles. In mammals 

 this property resides in the follicle-stimu- 

 lating hormone as we know it and, in lower 

 vertebrates, in a follicle-stimulating compo- 

 nent of the hypophyseal complex. In mam- 

 mals FSH acts on the ovary to promote the 

 development of primary follicles into large 

 fluid-filled vesicular structures of the type 

 that engaged the attention of de Graaf in 

 his search for the ovum. Primary follicles* 

 consist of a large oocyte surrounded by a 

 single layer of flattened granulosal cells. As 

 development proceeds, additional layers (6 

 to 9) of granulosa cells are proliferated to 

 form a spherical mass with the ovum at the 

 center. It is at this stage that the follicle • 

 becomes overtly sensitive to the action of 

 FSH. Its further development, including the 

 secretion of the follicular liquor, the mitotic 

 proliferation of granulosa cells, and the 

 molding of surrounding stroma into an in- 

 vesting layer of thecal cells, seems to be 

 largely controlled by FSH. In all mammals 

 studied, the growth and maturation of the 

 ovum itself seems independent of the action 

 of this hormone. In the monkey (Green and 

 Zuckerman, 1947), rat (Mandl and Zuck- 

 erman, 1952), and hamster (Knigge and 

 Leathem, 1956) the ovum reaches its full 

 size well before the appearance of the fol- 

 licular antrum. 



FSH, by promoting follicular enlarge- 

 ment, controls to a large degree the growth 

 of the ovary. In immature animals injected 

 with different amounts of FSH, the weight 

 of the ovary can be taken as a measure of 

 FSH activity, providing the hormone in- 

 jected is pure. The size to which the ovary 

 can be forced to develop in either immature 

 or adult mammals seems limited only by the 

 number of responsive follicles available. 

 With excessive dosage over periods of 5 to 

 10 or more days, ovaries of massive size 

 have been developed in many species of 

 birds (Witschi, 1955) and mammals (Ca- 



