The gonadotrophins

Follicle stimulating hormone (FSH), luteinizing hormone (LH) and human chorionic gonadotrophin (hCG) 

Luteinizing hormone (LH) Pituitary enhanced spermatogenesis (male) Induction of ovulation (female), synthesis 

Chorionic gonadotrophin (CG) of testosterone (male) Maintenance of the corpus luteum in 

Pregnant mare serum gonadotrophin Endometrial cups pregnant females Maintenance of pregnancy in equids 

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Mammalian cell culture is more technically complex and more expensive than microbial cell fermentation. Therefore, it is usually only used in the manufacture of therapeutic proteins that show extensive and essential post-translational modifications. In practice, this usually refers to glycosylation, and the use of animal cell culture would be appropriate where the carbohydrate content and pattern are essential to the protein s biological activity, its stability or serum half-life. Therapeutic proteins falling into this category include EPO (Chapter 10), the gonadotrophins (Chapter 11), some cytokines (Chapters 8-10) and intact monoclonal antibodies (Chapter 13). 

True endocrine hormones, however, remain a fairly well defined group. Virtually all of the hormones used therapeutically (discussed below) fit into this grouping. Examples include insulin, glucagon, GH and the gonadotrophins. 

The gonadotrophins are a family of hormones for which the gonads represent their primary target (Table 11.8). They directly and indirectly regulate reproductive function and, in some cases, the development of secondary sexual characteristics. Insufficient endogenous production of any... 

Table 11.8 The gonadotrophins, their site of synthesis and their major biological effects...

The oligosaccharide components play a direct and central role in the biosynthesis, secretion, serum half-life and potency of the gonadotrophins. The sugar components attached to the a-subu-nits play an important role in dimer assembly and stability, as well as hormone secretion and possibly signal transduction. The sugars associated with the P-subunit, while contributing to dimer assembly and secretion, appear to play a more prominent role in clearance of the hormone from circulation. 

Pregnant mare serum gonadotrophin (PMSG) is a unique member of the gonadotrophin family of hormones. It is synthesized only by pregnant mares (i.e. is not found in other species). Furthermore, it displays both FSH-like and LH-like biological activities. 

The causes of variability of superovulatory responses are complex and not fully understood. The general health of the animal, as well as its characteristic reproductive physiology, is important. The exact composition of the gonadotrophin preparations administered and the exact administration protocol also influence the outcome. The variability of FSH LH ratios in many p-FSH preparations can affect the results obtained, with the most consistent superovulatory responses being observed when FSH preparations exhibiting low LH activity are used. The availability of recombinant FSH and LH will overcome these difficulties at least. 

Figure 19.11 Hormones secreted by the hypothalamus, anterior pituitary, ovary and testis and feedback regulation. GnRH is gonadotrophin-releasing hormone the gonadotrophins are follicle-stimulating hormone (FSH) and luteinising hormone (LH). The effect of these hormones on activities in the ovary and testes is shown. FSH stimulates synthesis and secretion of oestradiol from follicle, and spermatogenesis in testis. LH stimulates synthesis and secretion of progesterone from corpus luteum and synthesis and secretion of testosterone by the Leydig cells.

Due to its probable direct effect on ovaries, it may increase the gonadotrophin secretion. It also exerts a weak estrogenic action on endometrium. 

Fig. 4. The gonadotrophin two-cell model of ovarian steroidogenesis involves the stimulation of thecal cells by LH to produce androstenedione and testosterone while FSH stimulates granulosa cells to synthesize estrogens from the theca-derived androgens.

U2. Ubaldi, F., Albano, C., Peukert, M., Riethmuller-Winzen, H., Camus, M., etal., Subtle progesterone rise after the administration of the gonadotrophin-releasing hormone antagonist cetrorelix in intracytoplasmic sperm injection cycles. Hum. Reprod. 11, 1405-1407 (1996). 

Q4 Hypothalamic hormones control the menstrual cycle via negative feedback loops. The hypothalamus produces gonadotrophin releasing hormone (GnRH), which stimulates secretion of the gonadotrophins FSH and LH from the anterior pituitary gland. 

Currie, W. Joseph, I. Rawlings, N. Morphine, naloxone and the gonadotrophin surge in ewes. Reprod. Fertil. 1991, 92, 407 14. 

Follicle-stimulating hormone (FSH) is one of the gonadotrophin hormones (with LH), secreted by the anterior pituitary gland and consists of double peptide chains. In women, in conjunction with LH, it causes the monthly ripening in one ovary of a follicle, and stimulates ovulation. In men it stimulates the production of sperm in the testes. It may be injected therapeutically in female infertility treatment to stimulate ovulation. It is available in several forms, e.g. urofollitrophin or menotrophin which is a 1 1 mix ofFSH/LH. 

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