Immunohistochemical localization of follicle-stimulating hormone, luteinizing hormone, growth hormone, adrenocorticotrophic hormone and prolactin in the human placenta

The sites of localization of luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), adrenocorticotrophic hormone (ACTH) and prolactin (PRL) within placental tissues have been studied by an immunoperoxidase technique. The syncytiotrophoblast is the sole significant site of localization of LH, FSH, GH and ACTH; PRL is found both in syncytiotrophoblast and in decidual cells. It is highly probable that the sites of localization of these peptide hormones represents their sites of synthesis in the placenta and thus that the syncytiotrophoblast is the sole site of synthesis of LH, FSH, LH and ACTH. PRL appears to be synthesized both in syncytiotrophoblast and decidua, but the latter is probably not the major site of synthesis of this hormone. Whether these placental peptide hormones have any physiological role to play during pregnancy or whether the placental capacity to synthesize such hormones is an atavistic phenomenon of no functional importance is currently a moot point.     

Luteinizing hormone releasing hormone analogue in treatment of hypergonadotrophic amenorrhoea

The effect of a luteinizing hormone releasing hormone analogue (HOE 766) was studied in four patients with hypergonadotrophic amenorrhoea (resistant ovary syndrome). After an initial phase of stimulation, there was a uniform and sustained suppression of gonadotrophin concentrations in all the patients during the 20-24 days of treatment, presumably due to down-regulation of the pituitary receptors. One patient ovulated after stopping treatment.     

Luteinizing hormone releasing hormone analogue in treatment of hypergonadotrophic amenorrhoea

Summary. The effect of a luteinizing hormone releasing hormone analogue (HOE 766) was studied in four patients with hypergonadotrophic amenorrhoea (resistant ovary syndrome). After an initial phase of stimulation, there was a uniform and sustained suppression of gonadotrophin concentrations in all the patients during the 20–24 days of treatment, presumably due to down-regulation of the pituitary receptors. One patient ovulated after stopping treatment.     

Luteinizing hormone and follicle-stimulating hormone responses to intransal gonadotropin-releasing hormone

For determination of the dose-response relationships of plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to the intranasal administration of gonadotropin-releasing hormone (GnRH), normal adult men were administered doses of 100, 200, 400, and 800 micrograms of GnRH on separate days, and plasma LH and FSH were measured before and after nasal insufflation of GnRH. Plasma LH was increased after a minimum dose of 200 micrograms GnRH. Median peak plasma LH levels occurred 30 minutes after intranasal GnRH and followed a log-dose relationship. When compared with intravenous GnRH, the biopotency of intranasal GnRH at the 200-, 400-, and 800-microgram doses was 1.1%, 2.3%, and 6.2%, respectively. Plasma FSH levels rose significantly only after the highest (800-micrograms) intranasal GnRH dose. From these data, we conclude that in eugonadal adult men the minimal effective dose of intranasal GnRH to elicit a significant pituitary (LH) response is 200 micrograms and that the relative efficacy of intranasal GnRH increases with the dose. In spite of the apparently low biopotency for intranasal GnRH, this route of administration may be considered as an alternative to the parenteral mode of GnRH delivery, and the lower biopotency can be partly overcome by increasing the dose.     

Assessment of luteinizing hormone level in the gonadotropin-releasing hormone antagonist protocol

In the GnRH-antagonist multiple-dose protocol, the LH level retrieved from a single measurement during ovarian stimulation and concomitant GnRH-antagonist administration can vary according to [1] the time point of sampling with respect to the GnRH-antagonist injection and [2] episodic changes in circulating LH concentration due to the pulsatile release of LH from the pituitary gland. To exemplify the size of pharmacodynamic effect of a single 0.25-mg cetrorelix administration on LH concentration profile and pulsatility, we measured endogenous LH levels every 15 minutes from 8 hours before the first cetrorelix administration until 24 hours thereafter on ovarian stimulation day 6 and 7 in a single patient.     

Gonadotropin-releasing hormone, follicle-stimulating hormone beta, luteinizing hormone beta gene structure in idiopathic hypogonadotropic hypogonadism.

OBJECTIVE: To determine if the genes for gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone beta (FSH beta), and luteinizing hormone beta (LH beta) are present, and if so, whether gene structure is normal in patients with idiopathic hypogonadotropic hypogonadism (IHH). DESIGN: Patients with clinical and laboratory characteristics of IHH were studied at the deoxyribonucleic acid (DNA) level to assess gene structure. SETTING: This study took place in an academic setting. PATIENTS: Human volunteers with documented IHH and fertile controls were studied. INTERVENTIONS: Genomic DNAs were extracted from each patient, Southern blots were constructed and hybridized to DNA probes for GnRH, FSH beta, and LH beta. DNA samples were also subjected to polymerase chain reaction analysis. MAIN OUTCOME MEASURES: Gene structure was assessed by analysis of autoradiographs and gel electrophoresis of polymerase chain reaction products in both the study patients and controls. RESULTS: Each analysis for FSH beta, LH beta, and GnRH demonstrated the same sized fragments in both the study group and control group. A 1.2-kilobase fragment containing the coding region for GnRH was present in all patients with IHH and controls by polymerase chain reaction. CONCLUSIONS: The genes for GnRH, LH beta, and FSH beta are present in patients with IHH. No large deletions or rearrangements of any of these genes were identified in any of these patients.     

Use of luteinizing hormone releasing hormone agonists in polycystic ovary syndrome

Luteinizing hormone releasing hormone (LHRH) agonists have been used in conjunction with gonadotrophins, and occasionally with pulsatile LHRH, for ovulation induction in women with clomiphene-citrate-resistant polycystic ovary syndrome (PCOS) and also for superovulation for in vitro fertilization (IVF) and gamete intrafallopian transfer in women with PCOS. In IVF, LHRH agonists given by the 'long protocol' before gonadotrophins are commenced have consistently shown higher pregnancy rates and higher live birth rates. Although the optimal time to commence LHRH agonist is not clearly determined, commencement in the early follicular phase possibly with pre-treatment with the combined oral contraceptive pill would avoid the risk of inadvertent administration during early pregnancy. The role of LHRH agonists in ovulation induction is less clear cut, although there may be some advantages in patients with refractory PCOS. The role of LHRH agonists in ovarian hyperstimulation syndrome and recurrent miscarriage is also discussed.     

Luteinizing hormone releasing hormone analogues for contraception

Peptide contraception based on LH-RH analogues is an interesting, fundamentally new lead to fertility control in women and men. A major advantage of using peptides instead of steroids for contraception is the fact that the hypothalamic peptides exert specific actions on the hypothalamic-pituitary-gonadal system and lack systemic effects. They are therefore less likely to cause metabolic derangements and other generalized adverse effects. Antagonistic analogues of LH-RH have been synthesized but until recently they have not been potent enough for clinical trials. However, chronic treatment with low doses of superactive stimulatory analogues of LH-RH paradoxically results in desensitization of the pituitary processes responsible for gonadotrophin release. This leads to a reversible inhibition of gonadal function. In women, ovulation can be inhibited by continuous intranasal LH-RH agonist treatment. In men, higher doses of LH-RH agonists have to be administered to suppress the gonadotrophin secretion enough to affect spermatogenesis. Optimal gonadotrophin suppression is, however, accompanied by a depression of the serum concentration of testosterone with loss of libido and impotence. The superagonists of LH-RH therefore have to be administered in combination with testosterone to induce oligo- or azoospermia without impotence. The overall results of clinical trials with superagonists of LH-RH for induction of inadequate corpus luteum function, luteolysis or early abortion in women are not impressive. The contraceptive effectiveness of these approaches to peptide contraception remains to be demonstrated in the human female. Inhibition of normal ovulation can, however, be consistently achieved by daily intranasal superagonist administration in women. This approach to fertility control has already been shown to provide safe and effective contraception in women.     

Luteinizing hormone supplementation increases pregnancy rates in gonadotropin-releasing hormone antagonist donor cycles

OBJECTIVE: To determine whether LH supplementation improved pregnancy and implantation rates in GnRH antagonist donor cycles. DESIGN: Donors were randomly assigned to a protocol using GnRH antagonist (GnRH-a) alone or GnRH-a + recombinant LH. Analysis of variance, Student's t-test and Fisher's exact test were used where appropriate. SETTING: Private clinical setting. PATIENT(S): Young voluntary donors with antagonist (n = 20) and antagonist + LH (n = 22). Fifty-five patients received oocytes. INTERVENTION(S): Donors received the GnRH-a (Cetrorelix, 0.25 mg/day) alone or in combination with recombinant LH (75 IU/day). Ovulation induction was carried out with recombinant FSH in a step-down protocol. The endometrial tissue of recipient patients was prepared with oral E(2) and P. MAIN OUTCOME MEASURE(S): Pregnancy and implantation rates in a donor program. RESULT(S): A significant increase in MII oocyte (80% vs. 71%), fertilization rates (83% vs. 71%), G1 embryos (17% vs. 3%), and implantation rates (35% vs. 15%), were found in recipients whose embryos originated from donors receiving GnRH-a + recombinant LH as compared to donors receiving GnRH-a alone. Estradiol levels, pregnancy/transfer and clinical pregnancies were lower (not significant) in donors treated with the GnRH-a alone vs. those receiving the recombinant LH-supplemented GnRH-a. CONCLUSION(S): The LH supplementation improved the possibilities of gestation for recipients whose embryos originated from GnRH-a-treated donors.     

Plasma hormone profile in anovulation

Daily plasma hormones, including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrone (E1), estradiol (E2), progesterone, androstenedione, and testosterone (T), were measured in 16 anovulatory patients for a span of 3 to 4 weeks. The clinical diagnoses in this group of patients included the following: anovulation-eumenorrhea (n = 5), anovulation-polymenorrhea (n = 1), anovulation-oligomenorrhea (n = 3), congenital adrenal hyperplasia (n = 1), polycystic ovarian disease (n = 4), severe hypothalamic amenorrhea (n = 1), and postpartum amenorrhea-galactorrhea (n = 1). Follicular activity was evident in polymenorrheic and oligomenorrheic patients, and menstruation occurred in these patients following estrogen withdrawal. No follicular maturation was noted in the group of patients with anovulation-eumenorrhea, and menstruation in these patients was considered breakthrough bleeding. Low FSH levels were observed in anovulatory patients with eumenorrhea, polymenorrhea, and oligomenorrhea. Significantly high LH values were noted in both classic and non-classic polycystic ovarian disease. Extremely low E1 and E2 levels were found in patients with severe hypothalamic amenorrhea and postpartum amenorrhea-galactorrhea. Slightly elevated progesterone levels were observed in polymenorrheic and oligomenorrheic patients prior to menstruation; this was frequently associated with an LH surge or elevation. Elevated T levels were consistently associated with hirsutism but not with obesity.     

Effects of human growth hormone upon term placental hormone secretion in vitro

The role of human growth hormone (hGH) on placental hormone secretion at term was investigated in two in vitro models: placental explants and cultured trophoblastic cells. Physiological concentrations of hGH caused a significant dose-dependent increase in placental lactogen and progesterone secretion. In the explant model it stimulated estradiol secretion. In order to determine whether this stimulatory effect on estradiol is exerted via aromatase, an isolated cell culture was utilized where androstenedione was supplied as substrate. In this model, hGH exerted a mild inhibitory effect. In conclusion, hGH at levels present in the fetal circulation exerts a significant stimulatory effect upon placental function as reflected by both peptide and steroid hormone production and secretion. The effect of estradiol secretion is the end result of an inhibitory effect on androgen aromatization and a stimulatory effect on earlier steps.     

Molecular composition of luteinizing hormone and follicle-stimulating hormone in commercial gonadotropin preparations

The biologic (B) and immunologic (I) properties of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied in three commercial urinary gonadotropin preparations and in the first international standard preparation of human urinary gonadotropins before and after fractionation by isoelectrofocusing (IEF). Significant differences were found in the IEF profiles of both bioactive and immunoreactive LH and FSH and in the B/I ratios of the preparations studied. The observed differences in the molecular composition of LH and FSH seem to be attributable to the purification procedures employed. The possible influence of these differences on the in vivo potencies, circulating half-lives, and clinical effects of gonadotropin preparations are discussed.     

Background of the development of the work in isolating interstitial cell-stimulating hormone (luteinizing hormone) and follicle-stimulating hormone

The background of the development of the work in isolating interstitial cell-stimulating hormone (ICSH) and follicle stimulating hormone (FSH) involved their isolation and purification. Ovine ICSH is a reversible dimer with monomeric molecular weight of 16,000 and consists of 2 subunits alpha and beta, each of which are individually inactive. The immunologic and biologic activity reside in the beta-subunit. The amino acid seuqences of ICSH-alpha and ICSH-beta are presented. The work on FSH is still in progress.